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Carboplatin and Paclitaxel Co...

Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer

Last Updated: 2014-09-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2013-12-31

Brief Summary

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This randomized phase II trial is studying how well giving carboplatin and paclitaxel together with cetuximab and/or cixutumumab (IMC-A12) 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.

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Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of patients with non-small cell lung cancer (NSCLC) randomized to carboplatin plus paclitaxel plus cetuximab or carboplatin plus paclitaxel plus cixutumumab (IMC-A12) or carboplatin plus paclitaxel plus cetuximab plus cixutumumab.

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 epidermal growth factor receptor (EGFR) by Immunohistochemistry (IHC), mutation, and gene copy number, Insulin-like growth factor 1 receptor (IGF-1R) and Insulin-like growth factor 2 receptor (IGF-2R) expression (both phosphorylated and unphosphorylated states), expression of p-AKT (ie, Protein Kinase B) 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 epidermal growth factor (EGF) and Transforming growth factor (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.

PROJECTED ACCRUAL: 200 patients

Conditions

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Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

carboplatin

Intervention Type DRUG

Given IV

paclitaxel

Intervention Type DRUG

Given IV

cetuximab

Intervention Type BIOLOGICAL

Given IV

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.

Group Type EXPERIMENTAL

cixutumumab

Intervention Type BIOLOGICAL

Given IV

carboplatin

Intervention Type DRUG

Given IV

paclitaxel

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

cixutumumab

Intervention Type BIOLOGICAL

Given IV

carboplatin

Intervention Type DRUG

Given IV

paclitaxel

Intervention Type DRUG

Given IV

cetuximab

Intervention Type BIOLOGICAL

Given IV

Interventions

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cixutumumab

Given IV

Intervention Type BIOLOGICAL

carboplatin

Given IV

Intervention Type DRUG

paclitaxel

Given IV

Intervention Type DRUG

cetuximab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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anti-IGF-1R recombinant monoclonal antibody IMC-A12 IMC-A12 Carboplat CBDCA JM-8 Paraplat Paraplatin Anzatax Asotax TAX Taxol C225 C225 monoclonal antibody IMC-C225 MOAB C225 monoclonal antibody C225

Eligibility Criteria

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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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* Ineligible for or refused treatment with bevacizumab
* No untreated or symptomatic central nervous system (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
* Absolute neutrophil count (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)
* Aspartate Aminotransferase (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
* Partial thromboplastin time (PTT) ≤ 1.2 times ULN and international normalized ratio (INR) ≤ 1.5 (unless patient is on anticoagulation therapy)
* 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 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
* 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
* 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

Exclusion Criteria

* Small cell lung cancer or mixed small cell and NSCLC
* History of allergic reactions attributed to compounds of similar chemical or biological composition to cixutumumab
* 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
* Prior agents targeting the EGFR or Insulin-like growth factor (IGFR) pathways
* Prior therapy for advanced NSCLC, except for surgery and/or radiotherapy
* Prior systemic therapy, including bevacizumab for advanced stage NSCLC
* Pregnant or nursing
* Peripheral neuropathy \> grade 1 as per Common Terminology Criteria for Adverse Event (CTCAE) v 4.0
* History of or suspected interstitial pneumonitis or pulmonary fibrosis on imaging
* 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
* Arterial thrombosis, pulmonary embolus, deep vein thrombosis, or hemorrhagic disorders within the past 28 days

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nasser Hanna

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

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Stanford University Hospitals and Clinics

Stanford, California, United States

Site Status

The Medical Center of Aurora

Aurora, Colorado, United States

Site Status

Boulder Community Hospital

Boulder, Colorado, United States

Site Status

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Site Status

Porter Adventist Hospital

Denver, Colorado, United States

Site Status

Exempla Saint Joseph Hospital

Denver, Colorado, United States

Site Status

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, United States

Site Status

Rose Medical Center

Denver, Colorado, United States

Site Status

Colorado Cancer Research Program CCOP

Denver, Colorado, United States

Site Status

Swedish Medical Center

Englewood, Colorado, United States

Site Status

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado, United States

Site Status

North Colorado Medical Center

Greeley, Colorado, United States

Site Status

Saint Anthony Hospital

Lakewood, Colorado, United States

Site Status

Sky Ridge Medical Center

Lone Tree, Colorado, United States

Site Status

Longmont United Hospital

Longmont, Colorado, United States

Site Status

McKee Medical Center

Loveland, Colorado, United States

Site Status

Saint Mary Corwin Medical Center

Pueblo, Colorado, United States

Site Status

North Suburban Medical Center

Thornton, Colorado, United States

Site Status

Exempla Lutheran Medical Center

Wheat Ridge, Colorado, United States

Site Status

Danbury Hospital

Danbury, Connecticut, United States

Site Status

Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

Manchester Memorial Hospital

Manchester, Connecticut, United States

Site Status

Medical Center of Central Georgia

Macon, Georgia, United States

Site Status

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status

Saint Joseph Medical Center

Bloomington, Illinois, United States

Site Status

Graham Hospital Association

Canton, Illinois, United States

Site Status

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status

Memorial Hospital

Carthage, Illinois, United States

Site Status

Eureka Hospital

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status

Evanston CCOP-NorthShore University HealthSystem

Evanston, Illinois, United States

Site Status

Illinois CancerCare Galesburg

Galesburg, Illinois, United States

Site Status

Illinois CancerCare-Havana

Havana, Illinois, United States

Site Status

Mason District Hospital

Havana, Illinois, United States

Site Status

Hinsdale Hematology Oncology Associates Incorporated

Hinsdale, Illinois, United States

Site Status

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status