Trial Outcomes & Findings for Erlotinib Hydrochloride With or Without Cixutumumab in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer (NCT NCT00778167)

Last Updated: 2014-05-21

Results Overview

Patients were evaluable for cohort dose escalation/de-escalation decision making either if they experienced DLTs in cycle 1 or if they had completed 24 of the planned 28 days (85%) dosing of erlotinib and three of the four planned days of weekly dosing of cixutumumab (75%) in cycle 1 in cohorts 1 and 2 in the absence of DLTs. In cohort 3, patients were evaluable for tolerability if they had completed 18 days (85%) dosing of erlotinib and had received the planned day 1 dose of cixutumumab.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

From time of first dose up to 28 days

Results posted on

2014-05-21

Participant Flow

Between December 2008 and October 2010, 18 patients were enrolled across cohorts 1 to 3.

Phase I of the study, determining a tolerable dose of IMC-A12 in combination with erlotinib, was completed. Because of concerns about the achievable dose intensity at the maximum tolerated dose, a randomized phase II study that would have involved Arm I in comparing full-dose erlotinib with the IMC-A12 in combination with erlotinib was cancelled.

Participant milestones

Participant milestones
Measure	Cohort 1 Cohort 1: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 6 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 2 Cohort 2: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 5 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 3 Cohort 3: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 15 mg/kg IV in 21-day cycles.
Overall Study STARTED	6	8	4
Overall Study COMPLETED	6	8	4
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Erlotinib Hydrochloride With or Without Cixutumumab in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=6 Participants Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 6 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 2 n=8 Participants Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 5 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 3 n=4 Participants Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 15 mg/kg IV in 21-day cycles.	Total n=18 Participants Total of all reporting groups
Age, Customized <=48 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Age, Customized Between 48 and 77 years	6 participants n=5 Participants	8 participants n=7 Participants	4 participants n=5 Participants	18 participants n=4 Participants
Age, Customized >=77 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	8 participants n=7 Participants	4 participants n=5 Participants	18 participants n=4 Participants

PRIMARY outcome

Timeframe: From time of first dose up to 28 days

Population: Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit and graded according to National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.

Outcome measures

Outcome measures
Measure	Cohort 1 n=6 Participants Cohort 1: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 6 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 2 n=8 Participants Cohort 2: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 5 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 3 n=4 Participants Cohort 3: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 15 mg/kg IV in 21-day cycles.
Safety and Tolerability of IMC-A12 in Combination With Erlotinib Hydrochloride as Graded by Common Terminology Criteria for Adverse Event (CTCAE) Version 3.0 (DLTs During Cycle One)	4 Participants	1 Participants	2 Participants

Adverse Events

Cohort 1

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 2

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Cohort 3

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. David R. Camidge

University of Colorado Denver

Phone: 720-848-0449

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Cohort 1 n=6 participants at risk Cohort 1: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 6 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 2 n=8 participants at risk Cohort 2: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 5 mg/kg IV on days 1, 8, 15, and 22 in 28-day cycles.	Cohort 3 n=4 participants at risk Cohort 3: Patients received oral erlotinib hydrochloride 150 mg once daily with cixutumumab 15 mg/kg IV in 21-day cycles.
General disorders Fatigue	83.3% 5/6 • Number of events 5 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	62.5% 5/8 • Number of events 5 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	75.0% 3/4 • Number of events 3 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Skin and subcutaneous tissue disorders Acneiform rash	33.3% 2/6 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	50.0% 4/8 • Number of events 4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	100.0% 4/4 • Number of events 4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Diarrhea	33.3% 2/6 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	50.0% 4/8 • Number of events 4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	75.0% 3/4 • Number of events 3 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Anorexia	33.3% 2/6 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 2/8 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Nausea	33.3% 2/6 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	50.0% 4/8 • Number of events 4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	12.5% 1/8 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	50.0% 2/4 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Mucositis	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	37.5% 3/8 • Number of events 3 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Respiratory, thoracic and mediastinal disorders Sinusitis	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	37.5% 3/8 • Number of events 3 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Taste alteration	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	37.5% 3/8 • Number of events 3 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Blood and lymphatic system disorders Hyperglycemia	16.7% 1/6 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 2/8 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
General disorders Rigors/chills	16.7% 1/6 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	12.5% 1/8 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Skin and subcutaneous tissue disorders Nail changes	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	12.5% 1/8 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Dehydration	16.7% 1/6 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/8 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Constipation	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	12.5% 1/8 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Gastrointestinal disorders Heartburn	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 2/8 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Renal and urinary disorders Renal failure	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	12.5% 1/8 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	25.0% 1/4 • Number of events 1 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Musculoskeletal and connective tissue disorders Muscle cramps	33.3% 2/6 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/8 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/4 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit
Nervous system disorders Dizziness	0.00% 0/6 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	0.00% 0/8 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit	50.0% 2/4 • Number of events 2 • Weekly through cycle 1 and on day 1 of each subsequent cycle Patients were evaluated with history, physical examination, vital signs, and blood tests weekly through cycle 1 and on day 1 of each subsequent cycle. Incidence and severity of AEs were collected at each study visit