Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT01708954

Recruitment Status : Active, not recruiting

First Posted : October 17, 2012

Results First Posted : December 1, 2016

Last Update Posted : May 16, 2024

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Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Recurrent Lung Non-Small Cell Carcinoma Stage IV Lung Non-Small Cell Cancer AJCC v7
Interventions	Drug: Cabozantinib S-malate Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis
Enrollment	125

Participant Flow

Recruitment Details	This study was activated on February 7, 2013 and closed to accrual on July 1, 2014 with final accrual of 125 patients. Among these, a total of 20 patients registered to Step 2.
Pre-assignment Details


Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)
Arm/Group Description	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...
Arm/Group Description	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Step 1
Started	42	40	43
Started Protocol Therapy	40	40	39
Eligible and Treated	38	38	35
Patients With MET Status Data Available	30	32	24
Completed	0 ^[1]	0 ^[1]	0 ^[1]
Not Completed	42	40	43
Reason Not Completed
Disease progression	26	17	14
Adverse Event	3	11	13
Death	3	2	3
Withdrawal by Subject	2	5	3
Other complicating disease	0	2	0
Crossed over to Step 2	2	0	0
Symptomatic deterioration	1	0	1
Off-treatment reason not submitted	1	1	1
Ineligible or never received treatment	4	2	8
[1] Treatment continued until progressive disease or unacceptable toxicity.
Period Title: Step 2
Started	13 ^[1]	7 ^[1]	0 ^[2]
Completed	0 ^[3]	0 ^[3]	0
Not Completed	13	7	0
Reason Not Completed
Disease progression	9	4	0
Adverse Event	3	2	0
Withdrawal by Subject	1	1	0
[1] Only patients with disease progression in Step 1 are eligible to register to Step 2. [2] Only patients with disease progression on Arms A and B were allowed to register to Step 2. [3] Treatment continued until progressive disease or unacceptable toxicity.

Baseline Characteristics

Arm/Group Title		Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)	Total
Arm/Group Description		Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...	Total of all reporting groups
Arm/Group Description		Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Number of Baseline Participants		38	38	35	111
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Eligible and treated patients
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	38 participants	38 participants	35 participants	111 participants
		68 (34 to 83)	65 (46 to 88)	63 (44 to 82)	66 (34 to 88)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	38 participants	38 participants	35 participants	111 participants
	Female	20 52.6%	24 63.2%	17 48.6%	61 55.0%
	Male	18 47.4%	14 36.8%	18 51.4%	50 45.0%

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival (PFS)
Description	PFS is defined as the time from randomization to documented disease pr...
Description	PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date of last disease assessment.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and treated patients


Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)
Arm/Group Description:	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...
Arm/Group Description:	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	38	38	35
Median (95% Confidence Interval) Unit of Measure: months
	1.8 (1.7 to 2.2)	4.3 (3.6 to 7.4)	4.7 (2.4 to 7.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Erlotinib), Arm C (Erlotinib+Cabozantinib)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 80% 0.25 to 0.53
	Estimation Comments	Hazard ratio of Arm C/Arm A

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A (Erlotinib), Arm B (Cabozantinib)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 80% 0.27 to 0.55
	Estimation Comments	Hazard ratio of Arm B/Arm A

2.Secondary Outcome


Title	Overall Survival (OS)
Description	OS is defined as the time from randomization to death from any cause o...
Description	OS is defined as the time from randomization to death from any cause or date of last known alive.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and treated patients


Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)
Arm/Group Description:	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...
Arm/Group Description:	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	38	38	35
Median (95% Confidence Interval) Unit of Measure: months
	5.1 (3.3 to 9.3)	9.2 (5.1 to 15.0)	13.3 ^[1] (7.6 to NA)

[1]

The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

3.Secondary Outcome


Title	Proportion of Patients With Objective Response
Description	Objective response is defined as complete response (CR) or partial res...
Description	Objective response is defined as complete response (CR) or partial response (PR) evaluated using RECIST v 1.1. CR is defined as disappearance of all lesions and any pathological lymph nodes must have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions and persistence of one or more non-target lesion(s).
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and treated patients


Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)
Arm/Group Description:	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...
Arm/Group Description:	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	38	38	35
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: proportion of participants
	0.03 (0.0009 to 0.141)	0.11 (0.03 to 0.25)	0.03 (0.001 to 0.15)

4.Secondary Outcome


Title	Proportion of Patients With MET Positivity
Description	Submission of archival tissue for central MET IHC testing was required...
Description	Submission of archival tissue for central MET IHC testing was required for this study, and total MET IHC testing was conducted at the Brigham and Women's Hospital using the c-Met clone CVD13 (arabbit polyclonal). Membranous and cytoplasmic staining were individually scored, and positivity was declared if MET was expressed in either the membrane or cytoplasm.
Time Frame	Assessed at baseline

Outcome Measure Data

Analysis Population Description

Eligible and treated patients who had sufficient samples for MET expression analysis.


Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)
Arm/Group Description:	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...
Arm/Group Description:	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	30	32	24
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: proportion of participants
	0.80 (0.61 to 0.92)	0.81 (0.64 to 0.93)	0.96 (0.79 to 0.999)

5.Secondary Outcome


Title	Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Assessed every 4 weeks while on treatment and for 30 days after the end of treatment

Outcome Measure Data

Analysis Population Description

All patients who received protocol therapy


Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)
Arm/Group Description:	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...
Arm/Group Description:	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	40	40	39
Measure Type: Number Number (90% Confidence Interval) Unit of Measure: Proportion of participants
	0.325 (0.204 to 0.466)	0.70 (0.560 to 0.817)	0.718 (0.577 to 0.833)

Adverse Events

Time Frame	Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)	Arm Z (Erlotinib+Cabozantinib; Step 2)
Arm/Group Description	Patients receive erlotinib 150mg PO...	Patients receive cabozantinib 60mg ...	Patients receive erlotinib 150mg PO...	Patients achieving disease progress...
Arm/Group Description	Patients receive erlotinib 150mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cabozantinib 60mg PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive erlotinib 150mg PO daily and cabozantinib 40mg PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients achieving disease progression in Arm A or Arm B may receive erlotinib 150mg and cabozantinib 40mg as patients in Arm C. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)	Arm Z (Erlotinib+Cabozantinib; Step 2)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)	Arm Z (Erlotinib+Cabozantinib; Step 2)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	13/40 (32.50%)	28/40 (70.00%)	28/39 (71.79%)	12/20 (60.00%)
Blood and lymphatic system disorders
Anemia ^† 1	1/40 (2.50%)	1/40 (2.50%)	1/39 (2.56%)	0/20 (0.00%)
Cardiac disorders
Atrial fibrillation ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Myocardial infarction ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Sinus tachycardia ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Diarrhea ^† 1	3/40 (7.50%)	3/40 (7.50%)	11/39 (28.21%)	8/20 (40.00%)
Ileus ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Mucositis oral ^† 1	0/40 (0.00%)	4/40 (10.00%)	1/39 (2.56%)	0/20 (0.00%)
Nausea ^† 1	1/40 (2.50%)	2/40 (5.00%)	1/39 (2.56%)	1/20 (5.00%)
Pancreatitis ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Vomiting ^† 1	1/40 (2.50%)	1/40 (2.50%)	1/39 (2.56%)	1/20 (5.00%)
Gastrointestinal disorders - Other, specify ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
General disorders
Fatigue ^† 1	5/40 (12.50%)	6/40 (15.00%)	6/39 (15.38%)	1/20 (5.00%)
Hepatobiliary disorders
Portal vein thrombosis ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Infections and infestations
Lung infection ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Skin infection ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Urinary tract infection ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Injury, poisoning and procedural complications
Fall ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Investigations
Aspartate aminotransferase increased ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Blood bilirubin increased ^† 1	1/40 (2.50%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Lipase increased ^† 1	1/40 (2.50%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Lymphocyte count decreased ^† 1	0/40 (0.00%)	1/40 (2.50%)	1/39 (2.56%)	0/20 (0.00%)
Neutrophil count decreased ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Platelet count decreased ^† 1	0/40 (0.00%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Weight loss ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Metabolism and nutrition disorders
Anorexia ^† 1	2/40 (5.00%)	1/40 (2.50%)	3/39 (7.69%)	1/20 (5.00%)
Dehydration ^† 1	1/40 (2.50%)	0/40 (0.00%)	1/39 (2.56%)	3/20 (15.00%)
Hypocalcemia ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Hypokalemia ^† 1	1/40 (2.50%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Hypomagnesemia ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Hyponatremia ^† 1	0/40 (0.00%)	1/40 (2.50%)	3/39 (7.69%)	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Bone pain ^† 1	0/40 (0.00%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Generalized muscle weakness ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Muscle weakness lower limb ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Nervous system disorders
Cognitive disturbance ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Dysphasia ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Intracranial hemorrhage ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Peripheral sensory neuropathy ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Syncope ^† 1	0/40 (0.00%)	0/40 (0.00%)	3/39 (7.69%)	0/20 (0.00%)
Psychiatric disorders
Confusion ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Insomnia ^† 1	1/40 (2.50%)	0/40 (0.00%)	0/39 (0.00%)	0/20 (0.00%)
Renal and urinary disorders
Proteinuria ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Reproductive system and breast disorders
Vaginal fistula ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	0/40 (0.00%)	2/40 (5.00%)	1/39 (2.56%)	0/20 (0.00%)
Pneumonitis ^† 1	0/40 (0.00%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Respiratory failure ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Rash acneiform ^† 1	1/40 (2.50%)	1/40 (2.50%)	2/39 (5.13%)	0/20 (0.00%)
Rash maculo-papular ^† 1	0/40 (0.00%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders - Other, specify ^† 1	0/40 (0.00%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Vascular disorders
Hypertension ^† 1	0/40 (0.00%)	10/40 (25.00%)	1/39 (2.56%)	0/20 (0.00%)
Hypotension ^† 1	0/40 (0.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
Thromboembolic event ^† 1	0/40 (0.00%)	3/40 (7.50%)	2/39 (5.13%)	2/20 (10.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE 4.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A (Erlotinib)	Arm B (Cabozantinib)	Arm C (Erlotinib+Cabozantinib)	Arm Z (Erlotinib+Cabozantinib; Step 2)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	35/40 (87.50%)	40/40 (100.00%)	38/39 (97.44%)	19/20 (95.00%)
Blood and lymphatic system disorders
Anemia ^† 1	6/40 (15.00%)	12/40 (30.00%)	13/39 (33.33%)	1/20 (5.00%)
Cardiac disorders
Atrial fibrillation ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Sinus tachycardia ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Endocrine disorders
Hyperthyroidism ^† 1	0/40 (0.00%)	5/40 (12.50%)	1/39 (2.56%)	0/20 (0.00%)
Hypothyroidism ^† 1	0/40 (0.00%)	10/40 (25.00%)	2/39 (5.13%)	1/20 (5.00%)
Endocrine disorders - Other, specify ^† 1	0/40 (0.00%)	1/40 (2.50%)	2/39 (5.13%)	0/20 (0.00%)
Eye disorders
Conjunctivitis ^† 1	3/40 (7.50%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Dry eye ^† 1	2/40 (5.00%)	2/40 (5.00%)	2/39 (5.13%)	0/20 (0.00%)
Watering eyes ^† 1	1/40 (2.50%)	1/40 (2.50%)	2/39 (5.13%)	0/20 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	4/40 (10.00%)	4/40 (10.00%)	4/39 (10.26%)	3/20 (15.00%)
Bloating ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Constipation ^† 1	1/40 (2.50%)	6/40 (15.00%)	4/39 (10.26%)	0/20 (0.00%)
Diarrhea ^† 1	24/40 (60.00%)	23/40 (57.50%)	31/39 (79.49%)	15/20 (75.00%)
Dry mouth ^† 1	3/40 (7.50%)	3/40 (7.50%)	6/39 (15.38%)	2/20 (10.00%)
Dyspepsia ^† 1	2/40 (5.00%)	4/40 (10.00%)	5/39 (12.82%)	0/20 (0.00%)
Dysphagia ^† 1	3/40 (7.50%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Flatulence ^† 1	0/40 (0.00%)	3/40 (7.50%)	1/39 (2.56%)	0/20 (0.00%)
Gastroesophageal reflux disease ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Mucositis oral ^† 1	2/40 (5.00%)	17/40 (42.50%)	9/39 (23.08%)	1/20 (5.00%)
Nausea ^† 1	8/40 (20.00%)	19/40 (47.50%)	17/39 (43.59%)	4/20 (20.00%)
Oral pain ^† 1	0/40 (0.00%)	2/40 (5.00%)	4/39 (10.26%)	1/20 (5.00%)
Proctitis ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Rectal hemorrhage ^† 1	0/40 (0.00%)	1/40 (2.50%)	2/39 (5.13%)	0/20 (0.00%)
Vomiting ^† 1	4/40 (10.00%)	5/40 (12.50%)	11/39 (28.21%)	1/20 (5.00%)
Gastrointestinal disorders - Other, specify ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	1/20 (5.00%)
General disorders
Chills ^† 1	1/40 (2.50%)	2/40 (5.00%)	0/39 (0.00%)	1/20 (5.00%)
Edema limbs ^† 1	0/40 (0.00%)	4/40 (10.00%)	1/39 (2.56%)	0/20 (0.00%)
Fatigue ^† 1	20/40 (50.00%)	27/40 (67.50%)	32/39 (82.05%)	13/20 (65.00%)
Fever ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	1/20 (5.00%)
Pain ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Infections and infestations
Paronychia ^† 1	0/40 (0.00%)	0/40 (0.00%)	2/39 (5.13%)	0/20 (0.00%)
Skin infection ^† 1	1/40 (2.50%)	2/40 (5.00%)	0/39 (0.00%)	1/20 (5.00%)
Upper respiratory infection ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Investigations
Alanine aminotransferase increased ^† 1	4/40 (10.00%)	21/40 (52.50%)	13/39 (33.33%)	4/20 (20.00%)
Alkaline phosphatase increased ^† 1	2/40 (5.00%)	8/40 (20.00%)	3/39 (7.69%)	2/20 (10.00%)
Aspartate aminotransferase increased ^† 1	8/40 (20.00%)	26/40 (65.00%)	17/39 (43.59%)	10/20 (50.00%)
Blood bilirubin increased ^† 1	5/40 (12.50%)	5/40 (12.50%)	4/39 (10.26%)	2/20 (10.00%)
Creatinine increased ^† 1	1/40 (2.50%)	5/40 (12.50%)	3/39 (7.69%)	1/20 (5.00%)
Lipase increased ^† 1	2/40 (5.00%)	1/40 (2.50%)	3/39 (7.69%)	2/20 (10.00%)
Lymphocyte count decreased ^† 1	1/40 (2.50%)	5/40 (12.50%)	5/39 (12.82%)	2/20 (10.00%)
Neutrophil count decreased ^† 1	0/40 (0.00%)	2/40 (5.00%)	2/39 (5.13%)	0/20 (0.00%)
Platelet count decreased ^† 1	1/40 (2.50%)	14/40 (35.00%)	8/39 (20.51%)	2/20 (10.00%)
Weight loss ^† 1	6/40 (15.00%)	13/40 (32.50%)	13/39 (33.33%)	5/20 (25.00%)
White blood cell decreased ^† 1	1/40 (2.50%)	9/40 (22.50%)	5/39 (12.82%)	0/20 (0.00%)
Metabolism and nutrition disorders
Anorexia ^† 1	11/40 (27.50%)	16/40 (40.00%)	19/39 (48.72%)	7/20 (35.00%)
Dehydration ^† 1	2/40 (5.00%)	2/40 (5.00%)	5/39 (12.82%)	0/20 (0.00%)
Hypercalcemia ^† 1	2/40 (5.00%)	0/40 (0.00%)	1/39 (2.56%)	0/20 (0.00%)
Hyperglycemia ^† 1	1/40 (2.50%)	3/40 (7.50%)	2/39 (5.13%)	0/20 (0.00%)
Hyperkalemia ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Hypoalbuminemia ^† 1	2/40 (5.00%)	9/40 (22.50%)	4/39 (10.26%)	3/20 (15.00%)
Hypocalcemia ^† 1	1/40 (2.50%)	4/40 (10.00%)	7/39 (17.95%)	0/20 (0.00%)
Hypokalemia ^† 1	4/40 (10.00%)	4/40 (10.00%)	7/39 (17.95%)	2/20 (10.00%)
Hypomagnesemia ^† 1	6/40 (15.00%)	13/40 (32.50%)	13/39 (33.33%)	2/20 (10.00%)
Hyponatremia ^† 1	3/40 (7.50%)	3/40 (7.50%)	3/39 (7.69%)	1/20 (5.00%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness ^† 1	0/40 (0.00%)	2/40 (5.00%)	4/39 (10.26%)	1/20 (5.00%)
Myalgia ^† 1	2/40 (5.00%)	1/40 (2.50%)	1/39 (2.56%)	0/20 (0.00%)
Nervous system disorders
Dizziness ^† 1	1/40 (2.50%)	3/40 (7.50%)	5/39 (12.82%)	0/20 (0.00%)
Dysgeusia ^† 1	6/40 (15.00%)	12/40 (30.00%)	11/39 (28.21%)	6/20 (30.00%)
Headache ^† 1	1/40 (2.50%)	2/40 (5.00%)	1/39 (2.56%)	0/20 (0.00%)
Lethargy ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Peripheral sensory neuropathy ^† 1	0/40 (0.00%)	5/40 (12.50%)	1/39 (2.56%)	0/20 (0.00%)
Psychiatric disorders
Anxiety ^† 1	0/40 (0.00%)	0/40 (0.00%)	2/39 (5.13%)	0/20 (0.00%)
Renal and urinary disorders
Chronic kidney disease ^† 1	0/40 (0.00%)	2/40 (5.00%)	1/39 (2.56%)	0/20 (0.00%)
Hematuria ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	1/20 (5.00%)
Proteinuria ^† 1	1/40 (2.50%)	13/40 (32.50%)	18/39 (46.15%)	0/20 (0.00%)
Renal and urinary disorders - Other, specify ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	2/40 (5.00%)	2/40 (5.00%)	3/39 (7.69%)	1/20 (5.00%)
Dyspnea ^† 1	1/40 (2.50%)	3/40 (7.50%)	6/39 (15.38%)	2/20 (10.00%)
Epistaxis ^† 1	1/40 (2.50%)	2/40 (5.00%)	1/39 (2.56%)	1/20 (5.00%)
Hoarseness ^† 1	0/40 (0.00%)	2/40 (5.00%)	2/39 (5.13%)	0/20 (0.00%)
Pneumonitis ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Sore throat ^† 1	1/40 (2.50%)	3/40 (7.50%)	0/39 (0.00%)	0/20 (0.00%)
Voice alteration ^† 1	1/40 (2.50%)	3/40 (7.50%)	3/39 (7.69%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	1/40 (2.50%)	2/40 (5.00%)	2/39 (5.13%)	1/20 (5.00%)
Dry skin ^† 1	9/40 (22.50%)	9/40 (22.50%)	10/39 (25.64%)	3/20 (15.00%)
Nail loss ^† 1	0/40 (0.00%)	0/40 (0.00%)	0/39 (0.00%)	1/20 (5.00%)
Palmar-plantar erythrodysesthesia syndrome ^† 1	3/40 (7.50%)	6/40 (15.00%)	6/39 (15.38%)	2/20 (10.00%)
Pruritus ^† 1	5/40 (12.50%)	2/40 (5.00%)	7/39 (17.95%)	1/20 (5.00%)
Rash acneiform ^† 1	23/40 (57.50%)	6/40 (15.00%)	25/39 (64.10%)	9/20 (45.00%)
Rash maculo-papular ^† 1	3/40 (7.50%)	4/40 (10.00%)	6/39 (15.38%)	3/20 (15.00%)
Skin hypopigmentation ^† 1	0/40 (0.00%)	2/40 (5.00%)	0/39 (0.00%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders - Other, specify ^† 1	0/40 (0.00%)	4/40 (10.00%)	3/39 (7.69%)	0/20 (0.00%)
Vascular disorders
Hypertension ^† 1	4/40 (10.00%)	10/40 (25.00%)	17/39 (43.59%)	4/20 (20.00%)
Thromboembolic event ^† 1	2/40 (5.00%)	1/40 (2.50%)	0/39 (0.00%)	0/20 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE 4.0

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

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Name/Title:	Study Statistician
Organization:	ECOG-ACRIN Statistical Office
Phone:	617-632-3012

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

Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN 1512 Investigators. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. doi: 10.1016/S1470-2045(16)30561-7. Epub 2016 Nov 4.

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01708954
Other Study ID Numbers:	NCI-2012-01938 NCI-2012-01938 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ECOG-E1512 CDR0000741879 E1512 ( Other Identifier: ECOG-ACRIN Cancer Research Group ) E1512 ( Other Identifier: CTEP ) U10CA180820 ( U.S. NIH Grant/Contract ) U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted:	October 15, 2012
First Posted:	October 17, 2012
Results First Submitted:	October 6, 2016
Results First Posted:	December 1, 2016
Last Update Posted:	May 16, 2024

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