Carboplatin and Paclitaxel Combined With Cetuximab and/or Cixutumumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
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Purpose
This randomized phase II trial is studying how well giving carboplatin and paclitaxel together with cetuximab and/or cixutumumab works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab and cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy together with monoclonal antibody therapy may kill more tumor cells. It is not yet known whether carboplatin and paclitaxel are more effective when given with cetuximab and/or cixutumumab in treating non-small cell lung cancer
| Condition | Intervention | Phase |
|---|---|---|
|
Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer |
Biological: cixutumumab Drug: carboplatin Drug: paclitaxel Biological: cetuximab Other: laboratory biomarker analysis |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Three-Arm Randomized Phase II Study of Carboplatin and Paclitaxel in Combination With Cetuximab, IMC-A12 or Both in Patients With Advanced Non-Small Cell Lung Cancer Who Will Not Receive Bevacizumab-Based Therapy |
- Progression-free survival (PFS) [ Time Frame: From randomization to death or disease progression, whichever occurs first, assessed up to 3 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Toxicity profile as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
| Enrollment: | 200 |
| Study Start Date: | September 2009 |
| Primary Completion Date: | April 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (carboplatin, paclitaxel, cetuximab)
Patients receive carboplatin IV over 15-30 minutes and paclitaxel IV over 3 hours on days 1 and 22 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cetuximab alone on days 1, 8, 15, 22, 29, and 36. Treatment with cetuximab repeats every 42 days in the absence of disease progression or unacceptable toxicity.
|
Drug: carboplatin
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Biological: cetuximab
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Arm II (carboplatin, paclitaxel, cixutumumab)
Patients receive carboplatin and paclitaxel as in arm I. Patients also receive cixutumumab IV over 1 hour on days 1, 15, and 29. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cixutumumab alone on days 1, 15, and 29. Treatment with cixutumumab repeats every 42 days in the absence of disease progression or unacceptable toxicity.
|
Biological: cixutumumab
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Arm III (carboplatin, paclitaxel, cetuximab, cixutumumab)
Patients receive carboplatin, paclitaxel, and cetuximab as in arm I. Patients also receive cixutumumab as in arm II. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cetuximab as in arm I and cixutumumab as in arm II.
|
Biological: cixutumumab
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Biological: cetuximab
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the progression-free survival of patients with NSCLC randomized to carboplatin plus paclitaxel plus cetuximab or carboplatin plus paclitaxel plus IMC-A12 (cixutumumab) or carboplatin plus paclitaxel plus cetuximab plus IMC-A12.
SECONDARY OBJECTIVES:
I. To evaluate the response rate, disease control rate (complete response plus partial response plus stable disease), and toxicities for each arm.
II. To evaluate EGFR by IHC, mutation, and gene copy number, IGF-1R and IGF-2R expression (both phosphorylated and unphosphorylated states), expression of p-AKT by IHC, and k-ras mutation.
III. Plasma-based biomarkers will be evaluated for total and free insulin-like growth factor 1 and 2, IGF-growth factor binding protein 3 (IGFBP3) and circulating levels of EGF and TGF alpha.
IV. To evaluate overall survival on each of the three arms.
OUTLINE: This is a multicenter study. Patients are stratified according to gender and histology (squamous cell vs non-squamous cell). Patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive carboplatin intravenously (IV) over 15-30 minutes and paclitaxel IV over 3 hours on days 1 and 22 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cetuximab alone on days 1, 8, 15, 22, 29, and 36. Treatment with cetuximab repeats every 42 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive carboplatin and paclitaxel as in arm I. Patients also receive cixutumumab IV over 1 hour on days 1, 15, and 29. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cixutumumab alone on days 1, 15, and 29. Treatment with cixutumumab repeats every 42 days in the absence of disease progression or unacceptable toxicity.
ARM III: Patients receive carboplatin, paclitaxel, and cetuximab as in arm I. Patients also receive cixutumumab as in arm II. Treatment repeats every 42 days for 2 courses. Patients with stable or responding disease after 2 courses proceed to maintenance therapy with cetuximab as in arm I and cixutumumab as in arm II.
Tumor tissue samples are collected at baseline for analysis of EGFR expression by IHC, mutation, and gene copy number; IGF-1R and IGF-2R expression (both phosphorylated and unphosphorylated states); p-AKT expression by IHC; and k-ras mutation. Blood, serum, and plasma samples are collected periodically for biomarker analysis.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
Stage IIIB disease
- T4, NX with nodule in ipsilateral lung lobe allowed provided patient is not a candidate for combined chemotherapy and radiotherapy
- Stage IV disease (includes M1a and M1b)
- Measurable disease as defined by RECIST criteria
- Ineligible for or refused treatment with bevacizumab
- No small cell lung cancer or mixed small cell and NSCLC
No untreated or symptomatic CNS metastases
Patients with a history of CNS metastases that are definitively treated, stable, and controlled are eligible provided the following criteria are met:
- Definitive therapy (surgery and/or radiotherapy) has been administered
- Not planning to undergo additional treatment for brain metastases
- Clinically stable
- Off corticosteroids or on a stable dose of corticosteroids for ≥ 14 days before study entry
- ECOG performance status 0-1
- Leukocytes > 3,000/mm^3
- ANC > 1,500/mm^3
- Hemoglobin > 9 g/dL
- Platelet count > 100,000/mm^3
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST < 3 times ULN (< 5 times ULN if elevations due to liver metastases)
- Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min
- Fasting serum glucose < 120 mg/dL
- PTT ≤ 1.2 times ULN and INR ≤ 1.5 (unless patient is on anticoagulation therapy)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after the last dose of cixutumumab
No poorly controlled diabetes mellitus
- Patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range and they are on a stable dietary or therapeutic regimen for this condition
- No peripheral neuropathy > grade 1 as per CTCAE v 4.0
- No history of or suspected interstitial pneumonitis or pulmonary fibrosis on imaging
No significant uncontrolled cardiac disease within the past 6 months, including any of the following:
- Uncontrolled hypertension (BP > 150/100 mm Hg)
- Unstable angina
- Recent myocardial infarction
- Uncontrolled congestive heart failure
- Cardiomyopathy with decreased ejection fraction
- No arterial thrombosis, pulmonary embolus, deep vein thrombosis, or hemorrhagic disorders within the past 28 days
No other prior or concurrent malignancy, except for the following:
- Curatively treated malignancy with no known active disease for ≥ 3 years AND is considered to be at low risk for recurrence by the treating physician
- Adequately treated nonmelanoma skin cancer or lentigo maligna with no evidence of disease
- Adequately treated cervical carcinoma in situ with no evidence of disease
- Prostatic intraepithelial neoplasia with no evidence of prostate cancer
- No history of any medical or psychiatric condition, addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study treatments or may interfere with the conduct of the study or interpretation of study results
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to cixutumumab
- Concurrent therapeutic anticoagulation allowed provided there is no bleeding and patient is on a stable dose of anticoagulation therapy (e.g., Warfarin with an INR of 2-3) for > 2 weeks prior to study entry
- No prior agents targeting the EGFR or IGFR pathways
- No prior therapy for advanced NSCLC, except for surgery and/or radiotherapy
- No prior systemic therapy, including bevacizumab for advanced stage NSCLC
- At least 21 days since prior radiotherapy
- More than 4 weeks since prior major surgery or hormonal therapy (other than hormone replacement therapy) and recovered
- More than 1 year since prior neoadjuvant or adjuvant chemotherapy
Contacts and Locations
Show 249 Study Locations| Principal Investigator: | Nasser Hanna | Eastern Cooperative Oncology Group |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00986674 History of Changes |
| Other Study ID Numbers: | NCI-2011-01976, E4508, U10CA021115 |
| Study First Received: | September 29, 2009 |
| Last Updated: | March 18, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Antibodies Antibodies, Monoclonal Cetuximab |
Carboplatin Paclitaxel Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic |
ClinicalTrials.gov processed this record on June 18, 2013