PD 0332991 and Cetuximab in Patients With Incurable SCCHN

• ClinicalTrials.gov Identifier: NCT02101034
• Recruitment Status: Completed
• First Posted: April 1, 2014
• Results First Posted: June 11, 2021
• Last Update Posted: December 21, 2023
• Sponsor: Washington University School of Medicine
• Collaborator: Pfizer
• Information provided by (Responsible Party): Washington University School of Medicine

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Squamous Cell of Head and Neck
• Interventions: Biological: Cetuximab; Drug: PD 0332991
• Enrollment: 96

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description	PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Period Title: Overall Study
Started	3	6	31	32	24
Completed	3	6	30	32	24
Not Completed	0	0	1	0	0
Reason Not Completed
Enrolled but did not start treatment	0	0	1	0	0

Baseline Characteristics

Arm/Group Title		Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:	Total
Arm/Group Description		PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	Total of all reporting groups
Overall Number of Baseline Participants		3	6	31	32	24	96
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	3 participants	6 participants	31 participants	32 participants	24 participants	96 participants
		62; (57 to 78)	61; (37 to 64)	64; (26 to 84)	64; (49 to 77)	66; (45 to 71)	63; (26 to 84)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	31 participants	32 participants	24 participants	96 participants
	Female	0 0.0%	2 33.3%	7 22.6%	11 34.4%	2 8.3%	22 22.9%
	Male	3 100.0%	4 66.7%	24 77.4%	21 65.6%	22 91.7%	74 77.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	31 participants	32 participants	24 participants	96 participants
	Hispanic or Latino	0 0.0%	0 0.0%	1 3.2%	1 3.1%	0 0.0%	2 2.1%
	Not Hispanic or Latino	3 100.0%	6 100.0%	30 96.8%	30 93.8%	23 95.8%	92 95.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	1 3.1%	1 4.2%	2 2.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	6 participants	31 participants	32 participants	24 participants	96 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 16.7%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	2 33.3%	7 22.6%	7 21.9%	0 0.0%	16 16.7%
	White	3 100.0%	3 50.0%	23 74.2%	24 75.0%	24 100.0%	77 80.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	1 3.2%	1 3.1%	0 0.0%	2 2.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	3 participants	6 participants	31 participants	32 participants	24 participants	96 participants
		3	6	31	32	24	96

Outcome Measures

1. Primary Outcome

Title	Phase I - Maximum Tolerated Dose (MTD)
Description	MTD is the dose level (DL) immediately below the DL at which 2 patients of a cohort experience dose limiting toxicity (DLT) in the 1st cycle (DLTs) Hematologic DLT is any of the below that occur during the 1st cycle that are possibly, probably, or definitely related to the treatment grade 4 neutropenia ≥7 days grade 4 infection with grade 3/4 neutropenia grade 4 thrombocytopenia with life-threatening bleeding treatment held for >14 days due to hematologic toxicity febrile neutropenia with temperature >=38.5°C Non-hematologic DLT is any possibly, probably, or definitely related grade 3 or 4 non-hematologic toxicity that occurs during the 1st except for suboptimally treated grade 3 or 4 nausea, vomiting, diarrhea, anorexia, or lymphopenia grade 3 metabolic abnormalities (limited to potassium, magnesium, and calcium) any hypersensitivity/infusion reaction or acneiform rash due to cetuximab treatment held for >14 days due to non-hematologic toxicity
Time Frame	6 months (estimated completion of Phase I)

Outcome Measure Data

Analysis Population Description

Only Phase I participants were evaluable for this outcome measure.

Arm/Group Title	Phase I: Dose Level 1 and Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description:	PD 0332991 will be administered on Days 1 through 21 of each 28 day cycle.; Dose Level 1 PD 0332991 100 mg per day; Dose Level 2 PD 0332991 125 mg per day Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	9	0	0	0
Measure Type: Number; Unit of Measure: mg
	NA [1]

[1]

None of the nine participants enrolled in the Phase I portion of the study experienced a dose-limiting toxicity. A MTD of palbociclib was not reached.

2. Primary Outcome

Title	Phase II: Efficacy as Measured by Overall Response Rate
Description	Tumor measurements will be collected at baseline, end of every even numbered cycles, and end of treatment. Measured by overall response rate (ORR=CR+PR) defined by RECIST criteria Best overall response is the best response recorded from the start of treatment until disease progression/recurrence Complete Response (CR) is defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters
Time Frame	End of treatment (estimated to be 12 months)

Outcome Measure Data

Analysis Population Description

Phase I participants were excluded from this outcome measure. 2 participants in Phase II Arm 1 were not evaluable due to early death and inability to measure the target lesion on the post-treatment non-contrast CT scan. 5 participants in Phase II Arm 2 were not evaluable due to comorbidity-related death (N=2), patient withdrawal (N=2), and non-treatment related adverse event (N=1).

Arm/Group Title	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description:	PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	0	0	28	27	24
Measure Type: Count of Participants; Unit of Measure: Participants
			11 39.3%	5 18.5%	1 4.2%

3. Secondary Outcome

Title	Phase I: Most Frequent Adverse Events
Description	Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame	Up to 30 days following completion of treatment (estimated to be 13 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I: Dose Level 1	Phase I: Dose Level 2
Arm/Group Description:	PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	3	6
Measure Type: Count of Participants; Unit of Measure: Participants
Grades 1-2 Neutropenia	1 33.3%	2 33.3%
Grade 3 Neutropenia	1 33.3%	2 33.3%
Grades 1-2 Anemia	2 66.7%	6 100.0%
Grade 3 Anemia	1 33.3%	0 0.0%
Grades 1-2 Thrombocytopenia	1 33.3%	3 50.0%
Grade 3 Thrombocytopenia	1 33.3%	0 0.0%
Grades 1-2 Fatigue	2 66.7%	3 50.0%
Grade 3 Fatigue	0 0.0%	0 0.0%
Grades 1-2 Nausea	0 0.0%	2 33.3%
Grade 3 Nausea	0 0.0%	0 0.0%
Grade 1-2 Vomiting	0 0.0%	1 16.7%
Grade 3 Vomiting	0 0.0%	0 0.0%
Grade 1-2 Diarrhea	1 33.3%	1 16.7%
Grade 3 Diarrhea	0 0.0%	0 0.0%
Grade 1-2 Infusion Reaction	0 0.0%	1 16.7%
Grade 3 Infusion Reaction	0 0.0%	0 0.0%
Grade 1-2 Acneiform Rash	2 66.7%	5 83.3%
Grade 3 Acneiform Rash	0 0.0%	0 0.0%
Grade 1-2 Hypomagnesemia	1 33.3%	2 33.3%
Grade 3 Hypomagnesemia	1 33.3%	0 0.0%

4. Secondary Outcome

Title	Phase II: PD 0332991 Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events
Description	Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame	Up to 30 days following completion of treatment (estimated to be 13 months)

Outcome Measure Data

Analysis Population Description

All arms of the Phase II Portion of the study were combined for this outcome measure as the treatment received was the same for each arm.

Arm/Group Title	Phase II Arm 1, Arm 2, and Arm 3
Arm/Group Description:	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	86
Measure Type: Count of Participants; Unit of Measure: Participants
Grades 1-2 platelet count decreased	50 58.1%
Grades 3-5 platelet count decreased	11 12.8%
Grades 1-2 neutrophil count decreased	28 32.6%
Grades 3-5 neutrophil count decreased	29 33.7%
Grades 1-2 white blood cell count decreased	43 50.0%
Grades 3-5 white blood cell count decreased	24 27.9%
Grades 1-2 electrocardiogram QT corrected interval prolonged	6 7.0%
Grades 3-5 electrocardiogram QT corrected interval prolonged	1 1.2%

5. Secondary Outcome

Title	Phase II: Cetuximab Related Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events
Description	Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame	Up to 30 days following completion of treatment (estimated to be 13 months)

Outcome Measure Data

Analysis Population Description

All arms of the Phase II Portion of the study were combined for this outcome measure as the treatment received was the same for each arm.

Arm/Group Title	Phase II Arm 1, Arm 2, and Arm 3
Arm/Group Description:	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	86
Measure Type: Count of Participants; Unit of Measure: Participants
Grades 1-2 acneiform rash	60 69.8%
Grades 3-5 acneiform rash	0 0.0%
Grades 1-2 hypomagnesemia	23 26.7%
Grades 3-5 hypomagnesemia	1 1.2%

6. Secondary Outcome

Title	Phase II: Adverse Events Occurring in 10% or More of Participants and All Grade 3-5 Adverse Events
Description	Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame	Up to 30 days following completion of treatment (estimated to be 13 months)

Outcome Measure Data

Analysis Population Description

All arms of the Phase II Portion of the study were combined for this outcome measure as the treatment received was the same for each arm.

Arm/Group Title	Phase II: Arm 1, Arm 2, and Arm 3
Arm/Group Description:	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	86
Measure Type: Count of Participants; Unit of Measure: Participants
Grades 1-2 fatigue	48 55.8%
Grades 3-5 fatigue	8 9.3%
Grades 1-2 hypoalbuminemia	37 43.0%
Grades 3-5 hypoalbuminemia	3 3.5%
Grades 1-2 anemia	44 51.2%
Grades 3-5 anemia	20 23.3%
Grades 1-2 hyponatremia	30 34.9%
Grades 3-5 hyponatremia	1 1.2%
Grades 1-2 hypertension	24 27.9%
Grades 3-5 hypertension	3 3.5%
Grades 1-2 nausea	30 34.9%
Grades 3-5 nausea	3 3.5%
Grades 1-2 dysphagia	30 34.9%
Grades 3-5 dysphagia	6 7.0%
Grades 1-2 dyspnea	29 33.7%
Grades 3-5 dyspnea	5 5.8%
Grades 1-2 hypocalcemia	19 22.1%
Grades 3-5 hypocalcemia	4 4.7%
Grades 1-2 lymphocyte count decreased	19 22.1%
Grades 3-5 lymphocyte count decreased	22 25.6%
Grades 1-2 diarrhea	21 24.4%
Grades 3-5 diarrhea	2 2.3%
Grades 1-2 weight loss	24 27.9%
Grades 3-5 weight loss	6 7.0%
Grades 1-2 AST increased	22 25.6%
Grades 3-5 AST increased	0 0.0%
Grades 1-2 tumor pain	18 20.9%
Grades 3-5 tumor pain	3 3.5%
Grades 1-2 constipation	15 17.4%
Grades 3-5 constipation	0 0.0%
Grades 1-2 cough	21 24.4%
Grades 3-5 cough	0 0.0%
Grades 1-2 anorexia	21 24.4%
Grades 3-5 anorexia	3 3.5%
Grades 1-2 vomiting	17 19.8%
Grades 3-5 vomiting	2 2.3%
Grades 1-2 dry mouth	13 15.1%
Grades 3-5 dry mouth	0 0.0%
Grades 1-2 sinus tachycardia	12 14.0%
Grades 3-5 sinus tachycardia	0 0.0%
Grades 1-2 alkaline phosphatase increased	12 14.0%
Grades 3-5 alkaline phosphatase increased	0 0.0%
Grades 1-2 hypokalemia	12 14.0%
Grades 3-4 hypokalemia	11 12.8%
Grades 1-2 hyperglycemia	11 12.8%
Grades 3-5 hyperglycemia	11 12.8%
Grades 1-2 hypernatremia	16 18.6%
Grades 3-5 hypernatremia	1 1.2%
Grades 1-2 fever	12 14.0%
Grades 3-5 fever	1 1.2%
Grades 1-2 dizziness	9 10.5%
Grades 3-5 dizziness	2 2.3%
Grades 1-2 hypercalcemia	9 10.5%
Grades 3-5 hypercalcemia	1 1.2%
Grades 1-2 dry skin	18 20.9%
Grades 3-5 dry skin	1 1.2%
Grades 1-2 dehydration	8 9.3%
Grades 3-5 dehydration	2 2.3%
Grades 1-2 hypotension	8 9.3%
Grades 3-5 hypotension	1 1.2%
Grades 1-2 creatinine increased	12 14.0%
Grades 3-5 creatinine increased	1 1.2%
Grades 1-2 trismus	7 8.1%
Grades 3-5 trismus	1 1.2%
Grades 1-2 elevated INR	6 7.0%
Grades 3-5 elevated INR	1 1.2%
Grades 1-2 dysarthria	5 5.8%
Grades 3-5 dysarthria	1 1.2%
Grades 1-2 hypophosphatemia	3 3.5%
Grades 3-5 hypophosphatemia	8 9.3%
Grades 1-2 lung infection	1 1.2%
Grades 3-5 lung infection	8 9.3%
Grades 1-2 febrile neutropenia	0 0.0%
Grades 3-5 febrile neutropenia	2 2.3%
Grade 1-2 abdominal pain	0 0.0%
Grades 3-5 abdominal pain	2 2.3%
Grades 1-2 colitis	0 0.0%
Grades 3-5 colitis	1 1.2%
Grades 1-2 tumor hemorrhage	0 0.0%
Grades 3-5 tumor hemorrhage	2 2.3%
Grades 1-2 hematuria	0 0.0%
Grades 3-5 hematuria	1 1.2%
Grades 1-2 duodenal ulcer	0 0.0%
Grades 3-5 duodenal ulcer	1 1.2%
Grades 1-2 esophageal fistula	0 0.0%
Grades 3-5 esophageal fistula	1 1.2%
Grades 1-2 oral cavity fistula	0 0.0%
Grades 3-5 oral cavity fistula	1 1.2%
Grades 1-2 sepsis	0 0.0%
Grades 3-5 sepsis	7 8.1%
Grades 1-2 duodenal perforation	0 0.0%
Grades 3-5 duodenal perforation	1 1.2%
Grades 1-2 skin infection	0 0.0%
Grades 3-5 skin infection	4 4.7%
Grades 1-2 tracheitis	0 0.0%
Grades 3-5 tracheitis	1 1.2%
Grades 1-2 aspiration	0 0.0%
Grades 3-5 aspiration	1 1.2%
Grades 1-2 pleural effusion	0 0.0%
Grades 3-5 pleural effusion	1 1.2%
Grades 1-2 pneumothorax	0 0.0%
Grades 3-5 pneumothorax	1 1.2%
Grades 1-2 catheter-related infection	0 0.0%
Grades 3-5 catheter-related infection	1 1.2%
Grades 1-2 jejunal obstruction	0 0.0%
Grades 3-5 jejunal obstruction	1 1.2%
Grades 1-2 mucositis oral	4 4.7%
Grades 3-5 mucositis oral	2 2.3%
Grades 1-2 oral hemorrhage	0 0.0%
Grades 3-5 oral hemorrhage	1 1.2%
Grade 5 death, not otherwise specified	3 3.5%
Grades 1-2 infusion-related reaction	0 0.0%
Grades 3-5 infusion-related reaction	1 1.2%
Grades 1-2 urinary tract infection	0 0.0%
Grades 3-5 urinary tract infection	2 2.3%
Grades 1-2 respiratory failure	0 0.0%
Grades 3-5 respiratory failure	2 2.3%
Grades 1-2 hypothyroidism	5 5.8%
Grades 3-5 hypothyroidism	0 0.0%
Grades 1-2 edema face	2 2.3%
Grades 3-5 edema face	1 1.2%
Grades 1-2 non-cardiac chest pain	2 2.3%
Grades 3-5 non-cardiac chest pain	1 1.2%
Grades 1-2 pancreatitis	0 0.0%
Grades 3-5 pancreatitis	1 1.2%
Grades 1-2 encephalopathy	0 0.0%
Grades 3-5 encephalopathy	1 1.2%
Grades 1-2 acute kidney injury	0 0.0%
Grades 3-5 acute kidney injury	1 1.2%
Grades 1-2 proteinuria	0 0.0%
Grades 3-5 proteinuria	1 1.2%
Grades 1-2 thromboembolic event	0 0.0%
Grades 3-5 thromboembolic event	1 1.2%

7. Secondary Outcome

Title	Phase II: Progression Free Survival (PFS)
Description	Participants were followed every 2 months for up to 5 years or until death, whichever occurs first. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description:	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	30	32	24
Median (95% Confidence Interval); Unit of Measure: months
	5.72; (3.97 to 7.93)	3.75; (2.93 to 4.37)	1.82; (1.77 to 2.10)

8. Secondary Outcome

Title	Phase II: Overall Survival (OS)
Description	Participants were followed every 2 months for up to 5 years or until death, whichever occurs first. Overall survival is measured from time of diagnosis to time of death.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description:	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	30	32	24
Median (95% Confidence Interval); Unit of Measure: months
	9.75; (5.57 to 15.53)	7.00; (4.97 to 9.37)	9.32; (4.39 to 18.35)

9. Secondary Outcome

Title	Phase II: Duration of Response
Description	Duration of overall response is measured from the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented.
Time Frame	Completion of treatment (estimated to be 12 months)

Outcome Measure Data

Analysis Population Description

Phase I participants were not evaluable for this outcome measure.

Arm/Group Title	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description:	PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
Overall Number of Participants Analyzed	0	0	11	5	1
Median (Inter-Quartile Range); Unit of Measure: months
			4.0; (1.8 to 5.6)	6.0; (2.0 to 15.5)	4.0

Adverse Events

Time Frame	Adverse events were followed from start of study treatment until 30 days following the last day of study treatment, up to approximately 13 months. All-Cause Morality was assessed from start of study treatment up to 5 years.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
Arm/Group Description	PD 0332991 100 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.	PD 0332991 125 mg per day will be administered on Days 1 through 21 of each 28 day cycle. Cetuximab will be administered intravenously on a weekly schedule. The first dose will be 400 mg/m2. The remaining weekly dose will be 250 mg/m2. Participants will continue to receive weekly cetuximab at 250 mg/m2 for the duration of their participation on study.
All-Cause Mortality
	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	6/6 (100.00%)	26/30 (86.67%)	19/32 (59.38%)	15/24 (62.50%)
Serious Adverse Events
	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/3 (66.67%)	4/6 (66.67%)	21/30 (70.00%)	16/32 (50.00%)	9/24 (37.50%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Cardiac disorders
Atrial fibrillation † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	1/3 (33.33%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Ascites † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Diarrhea † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Duodenal obstruction † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Duodenal perforation † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Duodenal ulcer † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Dysphagia † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	1/24 (4.17%)
Esophageal fistula † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Jejunal obstruction † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Nausa † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Oral cavity fistula † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Oral hemorrhage † 1	0/3 (0.00%)	1/6 (16.67%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Pancreatitis † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Vomiting † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
General disorders
Death NOS † 1	0/3 (0.00%)	0/6 (0.00%)	3/30 (10.00%)	0/32 (0.00%)	0/24 (0.00%)
Edema limbs † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Failure to thrive † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Fall † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	2/32 (6.25%)	0/24 (0.00%)
Fatigue † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Fever † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	2/24 (8.33%)
Infusion related reaction † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Immune system disorders
Allergic reaction † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Infections and infestations
Catheter related infection † 1	0/3 (0.00%)	1/6 (16.67%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Influenza † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Lung infection † 1	0/3 (0.00%)	1/6 (16.67%)	8/30 (26.67%)	3/32 (9.38%)	3/24 (12.50%)
Meningitis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Sepsis † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	3/32 (9.38%)	1/24 (4.17%)
Skin infection † 1	0/3 (0.00%)	1/6 (16.67%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Tracheitis † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Upper respiratory infection † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Urinary tract infection † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	1/24 (4.17%)
Wound infection † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Injury, poisoning and procedural complications
Hip fracture † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Intestinal stoma leak † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Metabolism and nutrition disorders
Anorexia † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Hypercalcemia † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	1/32 (3.13%)	0/24 (0.00%)
Hypokalemia † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Musculoskeletal and connective tissue disorders
Facial muscle weakness † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	2/32 (6.25%)	0/24 (0.00%)
Nervous system disorders
Encephalopathy † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Psychiatric disorders
Confusion † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	1/24 (4.17%)
Respiratory, thoracic and mediastinal disorders
Aspiration † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Dyspnea † 1	1/3 (33.33%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	1/24 (4.17%)
Hypoxia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Laryngeal hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Pharyngeal hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Pneumothorax † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Respiratory failure † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Vascular disorders
Thromboembolic event † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Phase I: Dose Level 1	Phase I: Dose Level 2	Phase II Arm 1: Platin-Resistant HPV-Unrelated SCCHN	Phase II Arm 2: Cetuximab-Resistant HPV-Unrelated SCCHN	Phase II Arm 3:
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	6/6 (100.00%)	30/30 (100.00%)	32/32 (100.00%)	24/24 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	3/3 (100.00%)	6/6 (100.00%)	30/30 (100.00%)	24/32 (75.00%)	17/24 (70.83%)
Febrile neutropenia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Cardiac disorders
Atrial fibrillation † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	1/24 (4.17%)
Constrictive pericarditis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Sinus bradycardia † 1	0/3 (0.00%)	0/6 (0.00%)	3/30 (10.00%)	1/32 (3.13%)	2/24 (8.33%)
Sinus tachycardia † 1	0/3 (0.00%)	2/6 (33.33%)	20/30 (66.67%)	12/32 (37.50%)	4/24 (16.67%)
Ear and labyrinth disorders
Ear pain † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Hearing imparied † 1	0/3 (0.00%)	0/6 (0.00%)	5/30 (16.67%)	1/32 (3.13%)	2/24 (8.33%)
Otorrhea † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Tinnitus † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	2/24 (8.33%)
Vertigo † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Endocrine disorders
Hyperthyroidism † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Hypoparathyroidism † 1	0/3 (0.00%)	0/6 (0.00%)	5/30 (16.67%)	0/32 (0.00%)	0/24 (0.00%)
Hypothrydodism † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	4/32 (12.50%)	5/24 (20.83%)
Eye disorders
Blurred vision † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	1/32 (3.13%)	0/24 (0.00%)
Conjuctivitis † 1	0/3 (0.00%)	0/6 (0.00%)	3/30 (10.00%)	2/32 (6.25%)	0/24 (0.00%)
Dry eye † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Eye discomfort † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Melanocytic nevus † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	3/32 (9.38%)	4/24 (16.67%)
Anal hemorrhage † 1	1/3 (33.33%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Ascites † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Colitis † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Constipation † 1	1/3 (33.33%)	1/6 (16.67%)	9/30 (30.00%)	6/32 (18.75%)	3/24 (12.50%)
Diarrhea † 1	1/3 (33.33%)	1/6 (16.67%)	12/30 (40.00%)	10/32 (31.25%)	3/24 (12.50%)
Dry mouth † 1	1/3 (33.33%)	3/6 (50.00%)	18/30 (60.00%)	13/32 (40.63%)	10/24 (41.67%)
Duodenal ulcer † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Dyspepsia † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	3/32 (9.38%)	1/24 (4.17%)
Dysphagia † 1	0/3 (0.00%)	3/6 (50.00%)	19/30 (63.33%)	13/32 (40.63%)	8/24 (33.33%)
Esophageal fistula † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Fecal incontinence † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Gastroesophageal reflux disease † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	2/32 (6.25%)	5/24 (20.83%)
Hemorrhoids † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Hypersalivation † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	2/32 (6.25%)	0/24 (0.00%)
Mouth sores † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Mucositis oral † 1	1/3 (33.33%)	0/6 (0.00%)	10/30 (33.33%)	5/32 (15.63%)	5/24 (20.83%)
Nausea † 1	0/3 (0.00%)	2/6 (33.33%)	10/30 (33.33%)	18/32 (56.25%)	7/24 (29.17%)
Odynophagia † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Oral bleeding † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	2/32 (6.25%)	0/24 (0.00%)
Oral cavity fistula † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Oral dysesthesia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	2/24 (8.33%)
Oral hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Oral pain † 1	2/3 (66.67%)	2/6 (33.33%)	1/30 (3.33%)	2/32 (6.25%)	3/24 (12.50%)
Rectal bleeding † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Sore tongue † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Vomiting † 1	0/3 (0.00%)	1/6 (16.67%)	5/30 (16.67%)	10/32 (31.25%)	3/24 (12.50%)
General disorders
Chills † 1	0/3 (0.00%)	0/6 (0.00%)	8/30 (26.67%)	5/32 (15.63%)	3/24 (12.50%)
Edema face † 1	0/3 (0.00%)	0/6 (0.00%)	4/30 (13.33%)	4/32 (12.50%)	3/24 (12.50%)
Edema limbs † 1	0/3 (0.00%)	0/6 (0.00%)	6/30 (20.00%)	2/32 (6.25%)	2/24 (8.33%)
Facial pain † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	2/24 (8.33%)
Fall † 1	0/3 (0.00%)	1/6 (16.67%)	4/30 (13.33%)	3/32 (9.38%)	2/24 (8.33%)
Fatigue † 1	2/3 (66.67%)	3/6 (50.00%)	26/30 (86.67%)	18/32 (56.25%)	17/24 (70.83%)
Fever † 1	0/3 (0.00%)	0/6 (0.00%)	6/30 (20.00%)	3/32 (9.38%)	1/24 (4.17%)
Flu like symptoms † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Hypothermia † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Infusion related reaction † 1	0/3 (0.00%)	1/6 (16.67%)	3/30 (10.00%)	0/32 (0.00%)	2/24 (8.33%)
Irritability † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Localized edema † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	1/32 (3.13%)	0/24 (0.00%)
Localized edema † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Malaise † 1	0/3 (0.00%)	0/6 (0.00%)	6/30 (20.00%)	3/32 (9.38%)	1/24 (4.17%)
Neck edema † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	1/24 (4.17%)
Non-cardiac chest pain † 1	0/3 (0.00%)	1/6 (16.67%)	5/30 (16.67%)	0/32 (0.00%)	3/24 (12.50%)
Pain † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	1/32 (3.13%)	1/24 (4.17%)
Pain in extremity † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	1/24 (4.17%)
Restless leg † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Upper back edema † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Immune system disorders
Allergic reaction † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Infections and infestations
Bone infection † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Bronchial infection † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Eye infection † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Folliculitis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Gastrointestinal infection † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Herpertic blepharitis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Lung infection † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Nail infection † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Otitis media † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Paronychia † 1	0/3 (0.00%)	1/6 (16.67%)	12/30 (40.00%)	5/32 (15.63%)	5/24 (20.83%)
Sepsis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Sinusitis † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	1/32 (3.13%)	0/24 (0.00%)
Skin infection † 1	1/3 (33.33%)	0/6 (0.00%)	6/30 (20.00%)	3/32 (9.38%)	1/24 (4.17%)
Upper respiratory infection † 1	1/3 (33.33%)	0/6 (0.00%)	2/30 (6.67%)	2/32 (6.25%)	1/24 (4.17%)
Urinary tract infection † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Wound infection † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Injury, poisoning and procedural complications
Bruising † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Hand wound † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Inguinal hernia † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Intestinal stoma leak † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Skin ulceration † 1	0/3 (0.00%)	0/6 (0.00%)	4/30 (13.33%)	0/32 (0.00%)	1/24 (4.17%)
Tracheal hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Investigations
Activated partial thromboplastin time prolonged † 1	1/3 (33.33%)	1/6 (16.67%)	5/30 (16.67%)	0/32 (0.00%)	0/24 (0.00%)
Alanine aminotransferase increased † 1	0/3 (0.00%)	2/6 (33.33%)	7/30 (23.33%)	1/32 (3.13%)	2/24 (8.33%)
Alkaline phosphatase increased † 1	0/3 (0.00%)	1/6 (16.67%)	7/30 (23.33%)	6/32 (18.75%)	7/24 (29.17%)
Aspartate aminotransferase increased † 1	0/3 (0.00%)	1/6 (16.67%)	10/30 (33.33%)	6/32 (18.75%)	6/24 (25.00%)
Blood bilirubin increased † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
CPK increased † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Cardiac troponin I increased † 1	0/3 (0.00%)	0/6 (0.00%)	3/30 (10.00%)	0/32 (0.00%)	0/24 (0.00%)
Cholesterol high † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	1/24 (4.17%)
Creatinine increased † 1	1/3 (33.33%)	2/6 (33.33%)	8/30 (26.67%)	2/32 (6.25%)	5/24 (20.83%)
Electrocardiogram QT corrected interval prolonged † 1	0/3 (0.00%)	0/6 (0.00%)	10/30 (33.33%)	2/32 (6.25%)	1/24 (4.17%)
GGT increased † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
INR increased † 1	1/3 (33.33%)	2/6 (33.33%)	15/30 (50.00%)	7/32 (21.88%)	4/24 (16.67%)
Lipase increased † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Lymphocyte count decreased † 1	3/3 (100.00%)	6/6 (100.00%)	28/30 (93.33%)	14/32 (43.75%)	19/24 (79.17%)
Neutrophil count decreased † 1	2/3 (66.67%)	4/6 (66.67%)	26/30 (86.67%)	18/32 (56.25%)	14/24 (58.33%)
Platelet count decreased † 1	2/3 (66.67%)	3/6 (50.00%)	23/30 (76.67%)	23/32 (71.88%)	16/24 (66.67%)
Weight loss † 1	0/3 (0.00%)	0/6 (0.00%)	15/30 (50.00%)	9/32 (28.13%)	8/24 (33.33%)
White blood cell decreased † 1	2/3 (66.67%)	6/6 (100.00%)	26/30 (86.67%)	23/32 (71.88%)	19/24 (79.17%)
Metabolism and nutrition disorders
Acidosis † 1	0/3 (0.00%)	0/6 (0.00%)	4/30 (13.33%)	3/32 (9.38%)	0/24 (0.00%)
Anorexia † 1	1/3 (33.33%)	2/6 (33.33%)	17/30 (56.67%)	6/32 (18.75%)	7/24 (29.17%)
Dehydration † 1	1/3 (33.33%)	1/6 (16.67%)	5/30 (16.67%)	5/32 (15.63%)	1/24 (4.17%)
Glucose intolerance † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	2/32 (6.25%)	0/24 (0.00%)
Hypercalcemia † 1	1/3 (33.33%)	0/6 (0.00%)	8/30 (26.67%)	4/32 (12.50%)	1/24 (4.17%)
Hyperglycemia † 1	1/3 (33.33%)	1/6 (16.67%)	10/30 (33.33%)	11/32 (34.38%)	1/24 (4.17%)
Hyperkalemia † 1	1/3 (33.33%)	0/6 (0.00%)	4/30 (13.33%)	3/32 (9.38%)	1/24 (4.17%)
Hyperlipidemia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	3/24 (12.50%)
Hypermagnesemia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Hypernatremia † 1	0/3 (0.00%)	0/6 (0.00%)	6/30 (20.00%)	5/32 (15.63%)	0/24 (0.00%)
Hypertriglyceridemia † 1	0/3 (0.00%)	1/6 (16.67%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Hypoalbuminemia † 1	3/3 (100.00%)	3/6 (50.00%)	20/30 (66.67%)	15/32 (46.88%)	7/24 (29.17%)
Hypocalcemia † 1	2/3 (66.67%)	4/6 (66.67%)	17/30 (56.67%)	7/32 (21.88%)	5/24 (20.83%)
Hypoglycemia † 1	1/3 (33.33%)	0/6 (0.00%)	5/30 (16.67%)	3/32 (9.38%)	1/24 (4.17%)
Hypokalemia † 1	0/3 (0.00%)	1/6 (16.67%)	13/30 (43.33%)	9/32 (28.13%)	2/24 (8.33%)
Hypomagnesemia † 1	2/3 (66.67%)	2/6 (33.33%)	13/30 (43.33%)	10/32 (31.25%)	5/24 (20.83%)
Hyponatremia † 1	1/3 (33.33%)	4/6 (66.67%)	22/30 (73.33%)	13/32 (40.63%)	5/24 (20.83%)
Hypophosphatemia † 1	1/3 (33.33%)	2/6 (33.33%)	7/30 (23.33%)	4/32 (12.50%)	2/24 (8.33%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	2/24 (8.33%)
Axilla pain † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Back pain † 1	0/3 (0.00%)	2/6 (33.33%)	9/30 (30.00%)	2/32 (6.25%)	4/24 (16.67%)
Clavicular pain † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Flank pain † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	1/24 (4.17%)
Generalized muscle weakness † 1	0/3 (0.00%)	0/6 (0.00%)	6/30 (20.00%)	2/32 (6.25%)	0/24 (0.00%)
Head soft tissue necrosis † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Hip pain † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Jaw pain † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Joint range of motion decreased cervical spine † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	2/32 (6.25%)	0/24 (0.00%)
Knee pain † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Kyphosis † 1	0/3 (0.00%)	0/6 (0.00%)	4/30 (13.33%)	1/32 (3.13%)	0/24 (0.00%)
Muscle weakness left sided † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Myalgia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	1/24 (4.17%)
Myositis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Neck pain † 1	0/3 (0.00%)	0/6 (0.00%)	9/30 (30.00%)	6/32 (18.75%)	3/24 (12.50%)
Osteonecrosis of jaw † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Osteonecrosis of lunate † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Shoulder pain † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Superficial soft tissue fibrosis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	2/32 (6.25%)	1/24 (4.17%)
Trismus † 1	1/3 (33.33%)	0/6 (0.00%)	6/30 (20.00%)	8/32 (25.00%)	4/24 (16.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Tumor pain † 1	0/3 (0.00%)	1/6 (16.67%)	8/30 (26.67%)	7/32 (21.88%)	3/24 (12.50%)
Nervous system disorders
Abdominal numbness † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Dizziness † 1	0/3 (0.00%)	0/6 (0.00%)	6/30 (20.00%)	9/32 (28.13%)	3/24 (12.50%)
Dysarthria † 1	1/3 (33.33%)	0/6 (0.00%)	9/30 (30.00%)	7/32 (21.88%)	4/24 (16.67%)
Dysgeusia † 1	0/3 (0.00%)	0/6 (0.00%)	3/30 (10.00%)	0/32 (0.00%)	1/24 (4.17%)
Encephalopathy † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Facial drooping † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	3/32 (9.38%)	0/24 (0.00%)
Facial palsy † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Headache † 1	0/3 (0.00%)	0/6 (0.00%)	9/30 (30.00%)	6/32 (18.75%)	3/24 (12.50%)
Hypersomnia † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Lethargy † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Memory impairment † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Movements involuntary † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Neuralgia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Peripheral sensory neuropathy † 1	0/3 (0.00%)	3/6 (50.00%)	7/30 (23.33%)	5/32 (15.63%)	1/24 (4.17%)
Presyncope † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Syncope † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	3/32 (9.38%)	0/24 (0.00%)
Psychiatric disorders
Agitation † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Anxiety † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	3/32 (9.38%)	2/24 (8.33%)
Confusion † 1	0/3 (0.00%)	0/6 (0.00%)	7/30 (23.33%)	1/32 (3.13%)	1/24 (4.17%)
Depression † 1	0/3 (0.00%)	1/6 (16.67%)	3/30 (10.00%)	4/32 (12.50%)	1/24 (4.17%)
Hallucinations † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	2/24 (8.33%)
Insomnia † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	3/24 (12.50%)
Renal and urinary disorders
Acute kidney injury † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	1/24 (4.17%)
Hematuria † 1	1/3 (33.33%)	0/6 (0.00%)	9/30 (30.00%)	4/32 (12.50%)	2/24 (8.33%)
Proteinuria † 1	0/3 (0.00%)	0/6 (0.00%)	7/30 (23.33%)	2/32 (6.25%)	1/24 (4.17%)
Urinary frequency † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Urinary retention † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	2/32 (6.25%)	1/24 (4.17%)
Urine discoloration † 1	0/3 (0.00%)	0/6 (0.00%)	3/30 (10.00%)	0/32 (0.00%)	0/24 (0.00%)
Reproductive system and breast disorders
Pelvic pain † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Vaginal hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Allergic Rhinitis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Aspiration † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	4/32 (12.50%)	0/24 (0.00%)
Atelectasis † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	2/24 (8.33%)
Bronchial obstruction † 1	0/3 (0.00%)	1/6 (16.67%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Chronic obstructive pulmonary disease † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Cough † 1	1/3 (33.33%)	2/6 (33.33%)	10/30 (33.33%)	11/32 (34.38%)	6/24 (25.00%)
Dyspnea † 1	0/3 (0.00%)	2/6 (33.33%)	19/30 (63.33%)	10/32 (31.25%)	8/24 (33.33%)
Epistaxis † 1	0/3 (0.00%)	0/6 (0.00%)	5/30 (16.67%)	5/32 (15.63%)	3/24 (12.50%)
Hemoptysis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Hiccups † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Hoarseness † 1	1/3 (33.33%)	0/6 (0.00%)	7/30 (23.33%)	4/32 (12.50%)	2/24 (8.33%)
Hypoxia † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	2/32 (6.25%)	0/24 (0.00%)
Laryngeal hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Laryngeal inflammation † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Laryngeal obstruction † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Left vocal cord paralysis † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Nasal congestion † 1	0/3 (0.00%)	1/6 (16.67%)	6/30 (20.00%)	3/32 (9.38%)	3/24 (12.50%)
Nasal regurgitation of liquids † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Oromaxillary fistula † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Pharyngeal fistula † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Pharyngeal hemorrhage † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Pleural effusion † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	4/32 (12.50%)	1/24 (4.17%)
Pneumothorax † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Postnasal drip † 1	1/3 (33.33%)	2/6 (33.33%)	2/30 (6.67%)	3/32 (9.38%)	1/24 (4.17%)
Productive cough † 1	0/3 (0.00%)	0/6 (0.00%)	13/30 (43.33%)	6/32 (18.75%)	5/24 (20.83%)
Respiratory failure † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Sleep apnea † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	2/24 (8.33%)
Sore throat † 1	0/3 (0.00%)	0/6 (0.00%)	7/30 (23.33%)	3/32 (9.38%)	2/24 (8.33%)
Voice alteration † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Wheezing † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	1/32 (3.13%)	0/24 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia † 1	0/3 (0.00%)	0/6 (0.00%)	8/30 (26.67%)	5/32 (15.63%)	2/24 (8.33%)
Bed sores † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Blisters on palms and toe † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Dermal neck nodules † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Dry skin † 1	2/3 (66.67%)	2/6 (33.33%)	18/30 (60.00%)	11/32 (34.38%)	10/24 (41.67%)
Erythema multiforme † 1	0/3 (0.00%)	0/6 (0.00%)	7/30 (23.33%)	3/32 (9.38%)	0/24 (0.00%)
Increased mucous secretions † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Lesion (unknown/furuncle) † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Nail loss † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	1/24 (4.17%)
Nail ridging † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Night sweats † 1	0/3 (0.00%)	0/6 (0.00%)	2/30 (6.67%)	0/32 (0.00%)	0/24 (0.00%)
Palmar-plantar erythrodysesthesia syndrome † 1	1/3 (33.33%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Periorbital edema † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Photosensitivity † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	0/32 (0.00%)	0/24 (0.00%)
Pruritus † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	2/32 (6.25%)	0/24 (0.00%)
Rash acneiform † 1	2/3 (66.67%)	5/6 (83.33%)	21/30 (70.00%)	15/32 (46.88%)	20/24 (83.33%)
Rash maculo-papular † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	3/32 (9.38%)	1/24 (4.17%)
Skin hyperpigmentation † 1	0/3 (0.00%)	0/6 (0.00%)	4/30 (13.33%)	3/32 (9.38%)	0/24 (0.00%)
Skin induration † 1	0/3 (0.00%)	0/6 (0.00%)	10/30 (33.33%)	6/32 (18.75%)	2/24 (8.33%)
Skin ulceration † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
Telangiectasia † 1	1/3 (33.33%)	0/6 (0.00%)	0/30 (0.00%)	0/32 (0.00%)	0/24 (0.00%)
Vascular disorders
Hematoma † 1	0/3 (0.00%)	0/6 (0.00%)	1/30 (3.33%)	1/32 (3.13%)	0/24 (0.00%)
Hypertension † 1	2/3 (66.67%)	4/6 (66.67%)	25/30 (83.33%)	13/32 (40.63%)	12/24 (50.00%)
Hypotension † 1	0/3 (0.00%)	0/6 (0.00%)	7/30 (23.33%)	5/32 (15.63%)	2/24 (8.33%)
Lymphedema † 1	0/3 (0.00%)	0/6 (0.00%)	4/30 (13.33%)	0/32 (0.00%)	1/24 (4.17%)
Thromboembolic event † 1	0/3 (0.00%)	0/6 (0.00%)	0/30 (0.00%)	1/32 (3.13%)	0/24 (0.00%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Douglas R. Adkins, M.D.
• Organization: Washington University School of Medicine
• Phone: 314-362-4471
• EMail: dadkins@wustl.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Adkins D, Ley J, Neupane P, Worden F, Sacco AG, Palka K, Grilley-Olson JE, Maggiore R, Salama NN, Trinkaus K, Van Tine BA, Steuer CE, Saba NF, Oppelt P. Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicentre, multigroup, phase 2 trial. Lancet Oncol. 2019 Sep;20(9):1295-1305. doi: 10.1016/S1470-2045(19)30405-X. Epub 2019 Jul 24.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02101034
• Other Study ID Numbers: 201404139
• First Submitted: March 27, 2014
• First Posted: April 1, 2014
• Results First Submitted: April 15, 2021
• Results First Posted: June 11, 2021
• Last Update Posted: December 21, 2023