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Safety And Efficacy Study Of Palbociclib Plus Cetuximab Versus Cetuximab To Treat Head And Neck Cancer

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ClinicalTrials.gov Identifier: NCT02499120
Recruitment Status : Completed
First Posted : July 15, 2015
Results First Posted : September 20, 2019
Last Update Posted : September 8, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Interventions Drug: palbociclib
Drug: Cetuximab
Drug: Placebo
Enrollment 125
Recruitment Details  
Pre-assignment Details A total of 125 participants were randomized; among them, 124 participants received study treatments. One (1) participant in the palbociclib + cetuximab treatment group was randomized but not treated.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes. Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Period Title: Overall Study
Started 65 60
Received Treatment 64 60
Completed 0 0
Not Completed 65 60
Reason Not Completed
Death             52             43
Lost to Follow-up             1             2
Participant refused further follow-up             1             0
Withdrawal by Subject             2             5
Other             9             10
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab Total
Hide Arm/Group Description Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes. Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes. Total of all reporting groups
Overall Number of Baseline Participants 65 60 125
Hide Baseline Analysis Population Description
Baseline analysis population included all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 60 participants 125 participants
58.3  (10.2) 60.9  (10.1) 59.5  (10.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 60 participants 125 participants
Female
8
  12.3%
4
   6.7%
12
   9.6%
Male
57
  87.7%
56
  93.3%
113
  90.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 65 participants 60 participants 125 participants
White
47
  72.3%
46
  76.7%
93
  74.4%
Black
1
   1.5%
1
   1.7%
2
   1.6%
Asian
15
  23.1%
13
  21.7%
28
  22.4%
Other
2
   3.1%
0
   0.0%
2
   1.6%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - randomization date +1)/30.4. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization had their OS times be censored at randomization. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.
Time Frame Baseline up to primary completion date (PCD) (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was intent-to-treat (ITT) population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 65 60
Median (95% Confidence Interval)
Unit of Measure: months
9.7
(7.3 to 13.9)
7.8
(6.7 to 10.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Cetuximab, Placebo + Cetuximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1800
Comments 1-sided p-value was from the log-rank test stratified by stratification factors ECOG(Eastern Cooperative Oncology Group) per randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.820
Confidence Interval (2-Sided) 95%
0.536 to 1.253
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever was earlier. Estimates of the PFS curves from the Kaplan Meier method were presented.
Time Frame Baseline up to PCD (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was intent-to-treat (ITT) population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 65 60
Median (95% Confidence Interval)
Unit of Measure: months
3.9
(3.6 to 5.6)
4.6
(2.3 to 5.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib + Cetuximab, Placebo + Cetuximab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4953
Comments 1-sided p-value was from the log-rank test stratified by stratification factors ECOG per randomization.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.000
Confidence Interval (2-Sided) 95%
0.669 to 1.495
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Objective Response (OR)
Hide Description OR was defined as the overall complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Objective response rate was defined as the proportion of participants with best overall response (BOR) of CR or PR relative to all randomized.
Time Frame Baseline up to PCD (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was ITT population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 65 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
27.7
(17.3 to 40.2)
25.0
(14.7 to 37.9)
4.Secondary Outcome
Title Percentage of Participants With Clinical Benefit Response (CBR)
Hide Description CBR was defined as the overall CR, PR, or stable disease>=24 weeks according to the RECIST version 1.1. Clinical benefit response rate was defined as the proportion of participants with CR, PR, or stable disease>= 24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline.
Time Frame Baseline up to PCD (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population was ITT population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 65 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
36.9
(25.3 to 49.8)
36.7
(24.6 to 50.1)
5.Secondary Outcome
Title Duration of Response (DR)
Hide Description DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1]/30.4.
Time Frame Baseline up to PCD (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
DR was only calculated for the subgroup of all ITT participants with an objective tumor response.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 18 15
Median (95% Confidence Interval)
Unit of Measure: months
7.6
(3.7 to 7.7)
7.4 [1] 
(3.6 to NA)
[1]
Number of participants with confirmed objective response was too small to provide such summary statistics (upper limit of 95% CI).
6.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events(TEAEs)
Hide Description AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. TEAEs were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time Frame From the first dose through and including 28 calendar days after the last administration of the study treatment (up to 6.9 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 64 60
Measure Type: Count of Participants
Unit of Measure: Participants
AEs (all causality)
61
  95.3%
56
  93.3%
AEs (treatment-related)
58
  90.6%
48
  80.0%
SAEs (all causality)
25
  39.1%
19
  31.7%
SAEs (treatment-related)
7
  10.9%
2
   3.3%
Grade 3 or 4 AEs (all causality)
33
  51.6%
19
  31.7%
Grade 5 AEs (all causality)
15
  23.4%
11
  18.3%
Grade 3 or 4 AEs (treatment-related)
34
  53.1%
10
  16.7%
Grade 5 AEs (treatment-related)
1
   1.6%
0
   0.0%
7.Secondary Outcome
Title Number of Participants With Laboratory Abnormalities
Hide Description The hematology, chemistry and coagulation tests were included in the laboratory examination. Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes. Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate and hemoglobin A1c (HbA1c). Coagulation evaluation included activated partial thromboplastin time/partial thromboplastin time, international normalized ratio (INR) or prothrombin time.
Time Frame From the Screening (Day -28) through and including 28 calendar days after the last administration of the study treatment (up to 7 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants with at least 1 observation of the laboratory test while on study treatment or during lag time.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 62 59
Measure Type: Count of Participants
Unit of Measure: Participants
61
  98.4%
55
  93.2%
8.Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Hide Description The EORTC QLQ-C30 is a 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global health/quality of life (QOL) subscale, and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation, and the financial impact of cancer). The questionnaire employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. For functional and global QOL scales, higher scores represented a better level of functioning and all scores were converted to a 0 to 100 scale. For symptom oriented scales, a higher score represented more severe symptoms, and all scores were converted to a 0-100 scale. Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.
Time Frame Baseline up to PCD (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all ITT participants, who had both baseline and at least 1 follow-up patient reported outcome (PRO) assessment before treatment discontinuation.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 57 55
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Global health status / QOL
2.82
(-1.49 to 7.13)
2.69
(-1.70 to 7.08)
Functional scale: Physical functioning
0.74
(-3.26 to 4.73)
-0.46
(-4.59 to 3.66)
Functional scale: Role functioning
-0.41
(-5.91 to 5.09)
-1.60
(-7.28 to 4.08)
Functional scale: Emotional functioning
4.16
(0.13 to 8.18)
3.56
(-0.57 to 7.69)
Functional scale: Cognitive functioning
-1.47
(-5.14 to 2.21)
-1.23
(-5.06 to 2.59)
Functional scale: Social functioning
1.24
(-4.43 to 6.90)
2.08
(-3.76 to 7.92)
Symptom scale/item: Fatigue
-2.79
(-7.04 to 1.46)
-5.12
(-9.50 to -0.75)
Symptom scale/item: Nausea and vomiting
-0.87
(-2.63 to 0.90)
-1.04
(-2.82 to 0.74)
Symptom scale/item: Pain
-5.98
(-11.06 to -0.90)
-6.10
(-11.32 to -0.87)
Symptom scale/item: Dyspnoea
3.07
(-2.15 to 8.30)
5.09
(-0.27 to 10.45)
Symptom scale/item: Insomnia
-4.62
(-10.33 to 1.08)
-5.02
(-10.88 to 0.84)
Symptom scale/item: Appetite loss
2.25
(-3.89 to 8.38)
-0.69
(-7.04 to 5.67)
Symptom scale/item: Constipation
-4.12
(-10.30 to 2.06)
-1.33
(-7.72 to 5.07)
Symptom scale/item: Diarrhoea
4.26
(1.34 to 7.17)
1.74
(-1.24 to 4.73)
Symptom scale/item: Financial difficulties
-5.26
(-11.61 to 1.10)
-0.27
(-6.83 to 6.29)
9.Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)
Hide Description The EORTC QLQ-H&N35 is designed to be used together with the core QLQ-C30. The recall period for the items in the module was "the past week". Items hn1 to hn30 were scored on 4 point Likert type categorical scales ("not at all", "a little", "quite a bit", "very much"). Items hn31 to hn35 had a "no/yes" response format. The scores were transformed into 0 to 100 scales, with a high score implying a high level of symptoms.Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.
Time Frame Baseline up to PCD (about 34 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all ITT participants, who had both baseline and at least 1 follow-up PRO assessment before treatment discontinuation.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 57 55
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Symptom scale/item: Pain
-3.57
(-8.56 to 1.43)
-0.41
(-5.54 to 4.73)
Symptom scale/item: Swallowing
-4.34
(-8.79 to 0.10)
-1.47
(-6.03 to 3.09)
Symptom scale/item: Senses problems
-1.58
(-7.22 to 4.05)
-1.88
(-7.72 to 3.96)
Symptom scale/item: Speech problems
-4.54
(-9.21 to 0.13)
-2.69
(-7.51 to 2.13)
Symptom scale/item: Trouble with social eating
-5.55
(-10.14 to -0.96)
-0.71
(-5.42 to 4.01)
Symptom scale/item: Trouble with social contact
-1.27
(-5.68 to 3.15)
3.45
(-1.14 to 8.04)
Symptom scale/item: Less sexuality
-3.32
(-11.44 to 4.80)
4.90
(-3.72 to 13.53)
Symptom scale/item: Teeth
-1.59
(-8.91 to 5.74)
-1.88
(-9.29 to 5.53)
Symptom scale/item: Opening mouth
0.35
(-5.29 to 5.99)
0.22
(-5.56 to 5.99)
Symptom scale/item: Dry mouth
-6.30
(-10.50 to -2.10)
3.44
(-0.82 to 7.71)
Symptom scale/item: Sticky saliva
-3.91
(-9.70 to 1.88)
4.68
(-1.22 to 10.58)
Symptom scale/item: Coughing
-3.99
(-8.67 to 0.69)
-1.72
(-6.48 to 3.04)
Symptom scale/item: Felt ill
1.320
(-4.22 to 6.86)
0.12
(-5.45 to 5.70)
Symptom scale/item: Pain killers
-13.18
(-24.49 to -1.88)
-11.39
(-23.02 to 0.24)
Symptom scale/item: Nutritional supplements
0.351
(-7.19 to 7.89)
-4.37
(-12.23 to 3.49)
Symptom scale/item: Feeding tube
-6.36
(-9.58 to -3.15)
-0.11
(-3.30 to 3.08)
Symptom scale/item: Weight loss
-17.72
(-27.23 to -8.21)
-9.47
(-19.16 to 0.22)
Symptom scale/item: Weight gain
-3.03
(-10.08 to 4.02)
5.16
(-1.96 to 12.27)
10.Secondary Outcome
Title Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)
Hide Description A central test was defined as the tumor tissue-based p16 IHC test performed at a central laboratory (Ventana). The analysis of concordance between HPV status as assessed by local or central laboratory included the number and percentage of participants with p16 detected or not detected at the central laboratory, given that all local testing must have been negative for HPV in order for the patient to be eligible for the study. Initial analysis of the p16 status was based on the conventional cutoff of 70% p16-positive tumor cells to call out cases that might be considered HPV-positive. P16 expression was scored as positive if strong and diffuse nuclear and cytoplasmic staining was present in at least 70% of the tumor cells.
Time Frame Screening
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants treated with cetuximab in combination with placebo or palbociclib who had at least 1 baseline biomarker assessment.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 54 48
Median (95% Confidence Interval)
Unit of Measure: months
PFS
3.7
(3.2 to 5.6)
5.0
(3.3 to 7.2)
OS
9.9
(7.1 to 13.9)
8.0
(7.0 to 14.7)
11.Secondary Outcome
Title Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%
Hide Description Rb expression in the palbociclib and cetuximab treatment group, the relationship of the biomarker (individually) with PFS and OS were explored using graphical methods such as box plots, at baseline. The tumors of participants were Rb-positive, which was defined by Rb IHC with>=1% positive tumor cells.
Time Frame Screening
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants treated with cetuximab in combination with placebo or palbociclib who had at least 1 baseline biomarker assessment.
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
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Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 57 53
Median (95% Confidence Interval)
Unit of Measure: months
PFS
3.9
(3.5 to 6.2)
4.6
(2.6 to 5.6)
OS
10.5
(7.1 to 15.6)
7.8
(6.9 to 11.8)
12.Secondary Outcome
Title Trough Plasma Concentration (Ctrough) and Within-participant Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib
Hide Description Ctrough is steady-state pre-dose concentration, which was observed directly from data. WPM-Ctrough is within-participant mean steady-state pre-dose concentration. For palbociclib, a steady-state trough was to be defined as a pre-dose plasma concentration following at least 7 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 24 hr +/- 2 hr and 24 min post-dose the day prior to PK collection and no more than 1 hr post-dose on the day of PK collection.
Time Frame Pre-dose of Day 15 in Cycle 1 and Cycle 2
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Hide Analysis Population Description
The analysis population included all as-treated participants, who were treated with the study treatments and had at least measured plasma concentration for at least 1 analyte (palbociclib and/or cetuximab)
Arm/Group Title Palbociclib + Cetuximab
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Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 57
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/ml)
Ctrough Cycle 1 Day 15 Number Analyzed 27 participants
69.8  (28.208)
Ctrough Cycle 2 Day 15 Number Analyzed 28 participants
67.8  (28.905)
WPM-Ctrough Number Analyzed 37 participants
71.6  (30.183)
13.Secondary Outcome
Title Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab
Hide Description Ctrough is steady-state pre-dose concentration. Cendinf is steady-state end-of-infusion concentration. Ctrough and Cendinf were observed directly from data. WPM-Ctrough and WPM-Cendinf are within-participant mean steady-state pre-dose concentration and end-of-infusion concentration. Acceptance criteria for a steady-state Cendinf was defined as a PK sample that was 1) collected after at least 3 consecutive weeks of cetuximab IV infusions without interruption or prior dose reduction and 2) was collected at the end of cetuximab infusion time +/- 10% of the actual duration of the cetuximab infusion.
Time Frame Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2
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Hide Analysis Population Description
The analysis population included all as-treated participants, who were treated with the study treatments and had at least measured plasma concentration for at least 1 analyte (palbociclib and/or cetuximab)
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description:
Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Overall Number of Participants Analyzed 57 57
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/ml
Ctrough Cycle 1 Day 15 Number Analyzed 51 participants 52 participants
39706.4
(92%)
42914.1
(62%)
Ctrough Cycle 2 Day 15 Number Analyzed 43 participants 43 participants
51005.3
(74%)
52995.7
(71%)
WPM-Ctrough Number Analyzed 54 participants 56 participants
45605.9
(83%)
46796.5
(63%)
Cendinf Cycle 1 Day 15 Number Analyzed 43 participants 40 participants
145748.3
(43%)
137185.5
(61%)
Cendinf Cycle 2 Day 15 Number Analyzed 37 participants 41 participants
149155.7
(38%)
153310.1
(39%)
WPM-Cendinf Number Analyzed 46 participants 50 participants
149119.2
(36%)
148063.3
(39%)
Time Frame From the first dose through and including 28 calendar days after the last administration of the study treatment (up to 6.9 years)
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
 
Arm/Group Title Palbociclib + Cetuximab Placebo + Cetuximab
Hide Arm/Group Description Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes. Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
All-Cause Mortality
Palbociclib + Cetuximab Placebo + Cetuximab
Affected / at Risk (%) Affected / at Risk (%)
Total   52/64 (81.25%)   43/60 (71.67%) 
Hide Serious Adverse Events
Palbociclib + Cetuximab Placebo + Cetuximab
Affected / at Risk (%) Affected / at Risk (%)
Total   25/64 (39.06%)   19/60 (31.67%) 
Blood and lymphatic system disorders     
Anaemia * 1  0/64 (0.00%)  1/60 (1.67%) 
Febrile neutropenia * 1  2/64 (3.13%)  0/60 (0.00%) 
Neutropenia * 1  1/64 (1.56%)  0/60 (0.00%) 
Cardiac disorders     
Cardiac arrest * 1  1/64 (1.56%)  0/60 (0.00%) 
Cardio-respiratory arrest * 1  1/64 (1.56%)  0/60 (0.00%) 
Gastrointestinal disorders     
Duodenal ulcer haemorrhage * 1  0/64 (0.00%)  1/60 (1.67%) 
Dysphagia * 1  0/64 (0.00%)  1/60 (1.67%) 
Large intestine perforation * 1  1/64 (1.56%)  0/60 (0.00%) 
Mouth haemorrhage * 1  1/64 (1.56%)  0/60 (0.00%) 
Nausea * 1  0/64 (0.00%)  1/60 (1.67%) 
General disorders     
Death * 1  1/64 (1.56%)  0/60 (0.00%) 
Disease progression * 1  7/64 (10.94%)  6/60 (10.00%) 
General physical health deterioration * 1  1/64 (1.56%)  0/60 (0.00%) 
Pyrexia * 1  1/64 (1.56%)  0/60 (0.00%) 
Immune system disorders     
Anaphylactic reaction * 1  0/64 (0.00%)  1/60 (1.67%) 
Infections and infestations     
Abscess * 1  0/64 (0.00%)  1/60 (1.67%) 
Lung abscess * 1  1/64 (1.56%)  0/60 (0.00%) 
Pneumonia * 1  4/64 (6.25%)  0/60 (0.00%) 
Pneumonia bacterial * 1  0/64 (0.00%)  1/60 (1.67%) 
Pulmonary tuberculosis * 1  0/64 (0.00%)  1/60 (1.67%) 
Sepsis * 1  0/64 (0.00%)  2/60 (3.33%) 
Pneumonia aspiration * 1  1/64 (1.56%)  0/60 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture * 1  1/64 (1.56%)  0/60 (0.00%) 
Hip fracture * 1  0/64 (0.00%)  1/60 (1.67%) 
Infusion related reaction * 1  1/64 (1.56%)  0/60 (0.00%) 
Investigations     
Neutrophil count decreased * 1  1/64 (1.56%)  0/60 (0.00%) 
Metabolism and nutrition disorders     
Dehydration * 1  1/64 (1.56%)  0/60 (0.00%) 
Hypoalbuminaemia * 1  0/64 (0.00%)  1/60 (1.67%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  0/64 (0.00%)  1/60 (1.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage * 1  1/64 (1.56%)  1/60 (1.67%) 
Nervous system disorders     
Coma * 1  1/64 (1.56%)  0/60 (0.00%) 
Seizure * 1  1/64 (1.56%)  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders     
Laryngeal obstruction * 1  1/64 (1.56%)  0/60 (0.00%) 
Pneumonitis * 1  1/64 (1.56%)  1/60 (1.67%) 
Pneumothorax * 1  0/64 (0.00%)  1/60 (1.67%) 
Pulmonary embolism * 1  1/64 (1.56%)  2/60 (3.33%) 
Pulmonary haemorrhage * 1  1/64 (1.56%)  1/60 (1.67%) 
Respiratory failure * 1  1/64 (1.56%)  0/60 (0.00%) 
1
Term from vocabulary, MedDRA 25.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Palbociclib + Cetuximab Placebo + Cetuximab
Affected / at Risk (%) Affected / at Risk (%)
Total   55/64 (85.94%)   53/60 (88.33%) 
Blood and lymphatic system disorders     
Anaemia * 1  23/64 (35.94%)  8/60 (13.33%) 
Leukopenia * 1  13/64 (20.31%)  0/60 (0.00%) 
Lymphopenia * 1  7/64 (10.94%)  1/60 (1.67%) 
Neutropenia * 1  19/64 (29.69%)  0/60 (0.00%) 
Thrombocytopenia * 1  5/64 (7.81%)  0/60 (0.00%) 
Gastrointestinal disorders     
Constipation * 1  7/64 (10.94%)  5/60 (8.33%) 
Diarrhoea * 1  9/64 (14.06%)  5/60 (8.33%) 
Dysphagia * 1  9/64 (14.06%)  5/60 (8.33%) 
Nausea * 1  8/64 (12.50%)  6/60 (10.00%) 
Stomatitis * 1  4/64 (6.25%)  0/60 (0.00%) 
Vomiting * 1  4/64 (6.25%)  1/60 (1.67%) 
General disorders     
Asthenia * 1  5/64 (7.81%)  7/60 (11.67%) 
Fatigue * 1  8/64 (12.50%)  8/60 (13.33%) 
Pyrexia * 1  9/64 (14.06%)  8/60 (13.33%) 
Infections and infestations     
Paronychia * 1  2/64 (3.13%)  8/60 (13.33%) 
Pneumonia * 1  4/64 (6.25%)  6/60 (10.00%) 
Investigations     
Alanine aminotransferase increased * 1  1/64 (1.56%)  5/60 (8.33%) 
Aspartate aminotransferase increased * 1  2/64 (3.13%)  4/60 (6.67%) 
Blood creatinine increased * 1  5/64 (7.81%)  3/60 (5.00%) 
Neutrophil count decreased * 1  9/64 (14.06%)  0/60 (0.00%) 
Platelet count decreased * 1  10/64 (15.63%)  0/60 (0.00%) 
Weight decreased * 1  5/64 (7.81%)  3/60 (5.00%) 
White blood cell count decreased * 1  11/64 (17.19%)  0/60 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  12/64 (18.75%)  10/60 (16.67%) 
Hyperglycaemia * 1  3/64 (4.69%)  5/60 (8.33%) 
Hypoalbuminaemia * 1  0/64 (0.00%)  4/60 (6.67%) 
Hypocalcaemia * 1  6/64 (9.38%)  1/60 (1.67%) 
Hypokalaemia * 1  6/64 (9.38%)  1/60 (1.67%) 
Hypomagnesaemia * 1  11/64 (17.19%)  8/60 (13.33%) 
Hyponatraemia * 1  4/64 (6.25%)  5/60 (8.33%) 
Musculoskeletal and connective tissue disorders     
Neck pain * 1  5/64 (7.81%)  4/60 (6.67%) 
Nervous system disorders     
Dizziness * 1  3/64 (4.69%)  6/60 (10.00%) 
Headache * 1  6/64 (9.38%)  5/60 (8.33%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  3/64 (4.69%)  5/60 (8.33%) 
Dyspnoea * 1  4/64 (6.25%)  8/60 (13.33%) 
Productive cough * 1  6/64 (9.38%)  4/60 (6.67%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform * 1  14/64 (21.88%)  13/60 (21.67%) 
Dry skin * 1  9/64 (14.06%)  2/60 (3.33%) 
Pruritus * 1  7/64 (10.94%)  4/60 (6.67%) 
Rash * 1  27/64 (42.19%)  21/60 (35.00%) 
Vascular disorders     
Hypertension * 1  5/64 (7.81%)  2/60 (3.33%) 
Hypotension * 1  3/64 (4.69%)  4/60 (6.67%) 
1
Term from vocabulary, MedDRA 25.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02499120    
Other Study ID Numbers: A5481044
2015-000515-41 ( EudraCT Number )
PALATINUS ( Other Identifier: Alias Study Number )
First Submitted: July 13, 2015
First Posted: July 15, 2015
Results First Submitted: June 23, 2019
Results First Posted: September 20, 2019
Last Update Posted: September 8, 2023