A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before

Study Overview
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Brief Summary
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The purpose of this study is to determine the number of participants whose cancer shrinks or disappears after treatment on the study.

Detailed Description
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Participants with Stage IIIb or IV non-small cell lung cancer (NSCLC) who have not received previous chemotherapy will be stratified, based on disease histology (squamous versus [vs.] nonsquamous).

Official Title
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Randomized, Open Label, Stratified Phase 2 Trial of Gemcitabine, Carboplatin, and Cetuximab With Vs. Without IMC-A12 in Chemotherapy-Naive Patients With Advanced/Metastatic Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Cisplatin
* Biological: IMC-A12 (cixutumumab)
* Biological: Cetuximab
* Biological: IMC-A12 (cixutumumab)
* Biological: Cetuximab
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has histologically or cytologically confirmed, Stage IIIb - IV NSCLC Has metastatic disease Has a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) Has adequate hematologic function Has adequate hepatic function Has adequate renal function Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Exclusion Criteria: Has uncontrolled brain metastases Has leptomeningeal disease Has received previous chemotherapy for NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization) Receiving any other investigational agent(s) Has a history of treatment with other agents targeting the insulin-like growth factor (IGF) or the epidermal growth factor (EGF) receptor Has a known allergy / history of hypersensitivity reaction to any of the treatment components Has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range [fasting glucose <160 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN) and hemoglobin A1C≤ 7%] and that they are on a stable dietary or therapeutic regimen for this condition Has an uncontrolled intercurrent illness Pregnant or lactating Has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years Has superior vena cava syndrome contraindicating hydration Has current clinically-relevant coronary artery disease (New York Heart Association III or IV) or uncontrolled congestive heart failure Has any National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version (v) 3.0 Grade ≥2 peripheral neuropathy Has significant third space fluid retention, requiring repeated drainage

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)<br>Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met *Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab) | Drug: Gemcitabine<br>* 1000 milligrams per square meter (mg/m^2) on Days 1 and 8 of each cycle [First 6 cycles (18 weeks)]<br>Drug: Cisplatin<br>* 75 mg/m^2 on Day 1 of each cycle [First 6 cycles (18 weeks)]<br>Biological: IMC-A12 (cixutumumab)<br>* 6 milligrams per kilogram (mg/kg) intravenous (IV) infusion, administered once per week (on Days 1, 8, and 15 of each cycle) [First 6 cycles (18 weeks)]<br>* Other names: LY3012217;Biological: Cetuximab<br>* 400 mg/m^2 IV infusion, administered on Day 1 of Cycle 1, 250 mg/m^2 once per week thereafter [First 6 cycles (18 weeks)]<br>* Other names: Erbitux®;Biological: IMC-A12 (cixutumumab)<br>* 10 mg/kg IV infusion, administered once every 2 weeks (Maintenance therapy)<br>* Other names: LY3012217;Biological: Cetuximab<br>* 500 mg/m^2 IV infusion, administered once every 2 weeks (Maintenance therapy)<br>* Other names: Erbitux®;Drug: Carboplatin<br>* Area under the curve (AUC) = 5, Day 1 of each cycle [First 6 cycles (18 weeks)] *Carboplatin will be replaced by Cisplatin<br>|
| Active Comparator: GCiC (Gemcitabine/Cisplatin/Cetuximab)<br>Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met *Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab) | Drug: Gemcitabine<br>* 1000 milligrams per square meter (mg/m^2) on Days 1 and 8 of each cycle [First 6 cycles (18 weeks)]<br>Drug: Cisplatin<br>* 75 mg/m^2 on Day 1 of each cycle [First 6 cycles (18 weeks)]<br>Biological: Cetuximab<br>* 400 mg/m^2 IV infusion, administered on Day 1 of Cycle 1, 250 mg/m^2 once per week thereafter [First 6 cycles (18 weeks)]<br>* Other names: Erbitux®;Biological: Cetuximab<br>* 500 mg/m^2 IV infusion, administered once every 2 weeks (Maintenance therapy)<br>* Other names: Erbitux®;Drug: Carboplatin<br>* Area under the curve (AUC) = 5, Day 1 of each cycle [First 6 cycles (18 weeks)] *Carboplatin will be replaced by Cisplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and the normalization of the tumour marker level. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants is calculated as a total number of participants with CR or PR / total number of participants treated * 100. | Randomization to measured progressive disease (PD) (up to 16.9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. | Randomization to death due to any cause or censor (up to 30.4 months) | 
| Progression-Free Survival (PFS) | PFS was defined as the duration from the date of randomization until disease progression or death due to any cause, whichever occurred first. Response was defined using RECIST, v 1.0 criteria. PD was defined as having a ≥20% increase in sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants who were alive and without disease progression, PFS was censored at the date of last objective tumor assessment. For participants who did not experience disease progression and were lost to follow-up, PFS was censored at the date of the last objective tumor assessment or the date of last contact. | Randomization to PD or death due to any cause or censor (up to 16.9 months) | 
| Time To Progression (TTP) | TTP was defined as the duration from the date of randomization until the date of disease progression. Response was defined using RECIST v 1.0 criteria. PD was defined as having a ≥20% increase in the sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants without disease progression, TTP was censored at the date of last objective tumor assessment. For participants without disease progression and were subsequently lost to follow-up, TTP was censored at the date of last follow-up visit or at the date of last contact. | Randomization to months until PD or censor (up to 16.9 months) | 
| Duration of Response | The duration of CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of disease progression or death. Response was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as having at least a 30% decrease in sum of LD of target lesions. Duration of response was censored on the date of last tumor assessment for participants who were alive and have no evidence of disease progression. | Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months) | 
| Number of Participants With Adverse Events (AEs) or Deaths | Data presented are the number of participants who experienced 1 or more AEs, serious AEs (SAEs), and AEs that lead to death during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this report. | Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up | 
| Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity) |  | Prior to first infusions of Cycles 1, 3, and 5 and 30 days following the end of therapy | 
| Maximum Concentration (Cmax) of Cixutumumab at Study Day 1 |  | Day 1 | 
| Cmax of Cixutumumab for Cycle 1 |  | Week 1 (Cycle 1, Day 1) | 
| Cmax of Cixutumumab for Cycle 3 |  | Week 7 (Cycle 3, Day 1) | 
| Cmax of Cixutumumab Cycle 5 |  | Week 13 (Cycle 5, Day 1) | 
| Minimum Concentration (Cmin) of Cixutumumab at Study Day 1 |  | Day 1 | 
| Cmin of Cixutumumab for Cycle 1 |  | Week 1 (Cycle 1, Day 1) | 
| Cmin of Cixutumumab for Cycle 3 |  | Week 7 (Cycle 3, Day 1) | 
| Cmin of Cixutumumab for Cycle 5 |  | Week 13 (Cycle 5, Day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumors, Antibodies, Monoclonal, Stage IIIb Metastatic Non-Small Cell Lung Cancer, Stage IV Metastatic Non-Small Cell Lung Cancer