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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00986674
First received: September 29, 2009
Last updated: September 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 (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.


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
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 [ Time Frame: Tumor measurements are repeated every 6 weeks while on treatment. After off treatment, assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3 ] [ Designated as safety issue: No ]

    Progression free survival is defined as time from registration to disease progression or death from any cause, whichever occurred earlier. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions .

    All eligible and treated patients were included in the analysis.



Secondary Outcome Measures:
  • Overall Survival [ Time Frame: assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3 ] [ Designated as safety issue: No ]
    Overall survival is defined as time from registration to death from any cause.

  • Response Rate [ Time Frame: Tumor measurements are repeated every 6 weeks while on treatment. After off treatment, assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3 ] [ Designated as safety issue: No ]
    Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Complete response (CR) was defined disappearance of all tumor lesions. Partial response (PR) was defined as as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. Overall response rate= CR+PR.


Enrollment: 140
Study Start Date: September 2009
Study Completion Date: December 2013
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
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
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

  Show Detailed Description

  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 249 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Nasser Hanna Indiana University School of Medicine
  More Information

Additional 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
Results First Received: September 19, 2014
Last Updated: September 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
Advanced Non-small Cell Lung Cancer
Carboplatin
Paclitaxel
Cetuximab
IMC-A12

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antibodies
Antibodies, Monoclonal
Carboplatin
Cetuximab
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Immunologic Factors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 21, 2014