Phase 2b Study of Cetuximab With Platinum-Based Chemo as First Line Treatment of Recurrent or Advanced NSCLC

Study Overview
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Brief Summary
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This study is testing the investigational drug, cetuximab, in combination with different chemotherapy drugs for lung cancer. The aim of the study is to determine which of the drug combinations looks most promising and should be tested further. The study will also look at what side effects may occur.

Official Title
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A Multi-Center Randomized Phase 2b Study of Cetuximab (Erbitux) in Combination With Platinum-Based Chemotherapy as First Line Treatment of Patients With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Paclitaxel
* Drug: Carboplatin
* Drug: Gemcitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent before study-related activities Histologically or cytologically confirmed Stage IIIb with cytologically documented malignant pleural or pericardial effusion, Stage IV, or recurrent non-smal cell lung cancer (NSCLC) after resection or radiation for earlier stage disease Measurable or evaluable disease (per modified Response Evaluation Criteria in Solid Tumors [RECIST] guidelines) Male or female ≥ 18 years of age Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 White blood count ≥ 3 x 10(9)/L with neutrophils ≥ 1.5 x 10(9)/L, platelet count ≥ 100 x 10(9)/L, and hemoglobin ≥ 9.5 g/dL Total bilirubin ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver mets Serum creatinine ≤ 1.25 x ULN Recovery from prior surgery or radiation to Grade 1 or better toxicity Women of childbearing potential (WOCBP) and fertile men with partners of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 wks after the study in such a manner that the risk of pregnancy is minimized WOCBP must have a negative serum or urine pregnancy test within 72 hrs prior to the start of study medication or in accordance with local regulations, whichever is of shorter duration Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and for up to 4 weeks after the study Women who are pregnant or breastfeeding Women with a positive pregnancy test during screening or prior to study drug administration Sexually active fertile men not using effective birth control if their partners are women of child-bearing potential Prior chemo for advanced NSCLC; neoadjuvant or post-operative adjuvant chemo is allowed if completed at least 12 months before study entry Previous exposure to epidermal growth factor receptor (EGFR)-targeted therapy. Prior treatment with monoclonal antibodies targeting receptors other than the EGFR, such as bevacizumab, is allowed if completed > 30 days prior to randomization Treatment with any investigational agent(s) within 4 weeks prior to study entry Concurrent anti-cancer therapy (chemotherapy, hormonal therapy, biologic or targeted therapy) other than protocol therapy Carcinoid, atypical carcinoid or small cell lung cancer Symptomatic or uncontrolled mets in the central nervous system Prior invasive malignancy requiring ongoing therapy within the past year Active infection (infection requiring intravenous [IV] antibiotics), including active tuberculosis, known and declared HIV Myocardial infarction within 6 months prior to study entry, uncontrolled congestive heart failure; or any current Grade 3 or 4 cardiovascular disorder despite treatment Known allergic/hypersensitivity reaction to any of the components of study treatments Peripheral neuropathy ≥ Grade 2, as assessed by Common Terminology Criteria for Adverse Events, version 3.0 History of significant neurologic or psychiatric disorders including but not limited to dementia, seizures, and bipolar disorder Medical or psychological condition that would not permit the patient to complete the study or sign informed consent Known drug abuse Patients of all races and ethnic groups are eligible for this trial.

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 |
| --- | --- |
| Active Comparator: Paclitaxel, Carboplatin, Cetuximab (Arm A)<br>Patients with squamous or non-squamous histologies will receive carboplatin and paclitaxel for a minimum of four and a maximum of six 21-day cycles, plus cetuximab, and then enter a maintenance phase with single-agent cetuximab. Cetuximab will be given on Day 1, and weekly during chemotherapy, followed by biweekly administration during the maintenance period. The choice of delivering four, five or six cycles of chemotherapy is at the investigator's discretion. | Drug: Cetuximab<br>* Cetuximab will be administered at a loading dose of 400 mg/m2 on Day 1, Cycle 1 and at a dose of 250 mg/m2 weekly during chemotherapy. During the maintenance period, cetuximab will be dosed at 500 mg/m2 every two weeks.<br>* Other names: Erbitux;Drug: Paclitaxel<br>* Paclitaxel 200 mg/m2 Day 1 every 21 days<br>* Other names: Taxol;Drug: Carboplatin<br>* Carboplatin AUC 6 Day 1 every 21 days<br>* Other names: Paraplatin;|
| Active Comparator: Platinum, Gemcitabine, Cetuximab (Arm B)<br>Patients with squamous or non-squamous histologies will receive gemcitabine with either carboplatin or cisplatin for a minimum of four and a maximum of six 21-day cycles, plus cetuximab, and then enter a maintenance phase with single-agent cetuximab. Cetuximab will be given on Day 1, and weekly during chemotherapy, followed by biweekly administration during the maintenance period. The choice of delivering four, five or six cycles of chemotherapy is at the investigator's discretion. The choice of platinum-based chemotherapy is also at the investigator's discretion. | Drug: Cetuximab<br>* Cetuximab will be administered at a loading dose of 400 mg/m2 on Day 1, Cycle 1 and at a dose of 250 mg/m2 weekly during chemotherapy. During the maintenance period, cetuximab will be dosed at 500 mg/m2 every two weeks.<br>* Other names: Erbitux;Drug: Carboplatin<br>* Carboplatin AUC 6 Day 1 every 21 days<br>* Other names: Paraplatin;Drug: Gemcitabine<br>* Gemcitabine 1,000 mg/m2 Days 1 and 8 every 21 days<br>* Other names: Gemzar;Drug: Cisplatin<br>* Cisplatin 75 mg/m2 Day I every 21 days<br>* Other names: Platinol;|
| Active Comparator: Platinum, Pemetrexed, Cetuximab (Arm C)<br>Patients with squamous histology will receive pemetrexed and either carboplatin or cisplatin for a minimum of four and a maximum of six 21-day cycles, plus cetuximab, and then enter a maintenance phase with single-agent cetuximab. Cetuximab will be given on Day 1, and weekly during chemotherapy, followed by biweekly administration during the maintenance period. The choice of delivering four, five or six cycles of chemotherapy is at the investigator's discretion. The choice of platinum-based chemotherapy is also at the investigator's discretion. Patients with non-squamous histology are not eligible for this arm. | Drug: Cetuximab<br>* Cetuximab will be administered at a loading dose of 400 mg/m2 on Day 1, Cycle 1 and at a dose of 250 mg/m2 weekly during chemotherapy. During the maintenance period, cetuximab will be dosed at 500 mg/m2 every two weeks.<br>* Other names: Erbitux;Drug: Carboplatin<br>* Carboplatin AUC 6 Day 1 every 21 days<br>* Other names: Paraplatin;Drug: Cisplatin<br>* Cisplatin 75 mg/m2 Day I every 21 days<br>* Other names: Platinol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival by Treatment Arm |  | Survival was measured from the date of randomization to date of death due to any cause, assessed up to 36 months. Subjects who were alive at the date of last contact were censored at the date of last contact. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year Survival by Treatment Arm |  | Survival was measured from the date of randomization to date of death due to any cause, assessed up to 36 months. Subjects who were alive at the date of last contact were censored at the date of last contact. | 
| Overall Survival by Histology |  | Survival was measured from the date of randomization to date of death due to any cause, assessed up to 36 months. Subjects who were alive at the date of last contact were censored at the date of last contact. |