Carboplatin and Paclitaxel Combined With Cetuximab and/or Cixutumumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00986674
First received: September 29, 2009
Last updated: March 19, 2014
Last verified: March 2014
  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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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: 140
Study Start Date: September 2009
Primary Completion Date: August 2013 (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:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00986674

  Show 249 Study Locations
Sponsors and Collaborators
Investigators
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, NCI-2011-01976, CDR0000655611, ECOG-E4508, E4508, E4508, U10CA021115
Study First Received: September 29, 2009
Last Updated: March 19, 2014
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 April 17, 2014