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Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
This study is not yet open for participant recruitment.
Verified by National Cancer Institute (NCI), September 2009
First Received: August 7, 2009   Last Updated: September 4, 2009   History of Changes
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00955305
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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 bevacizumab 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. It is not yet known whether giving combination chemotherapy together with bevacizumab is more effective when given with or without cixutumumab in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase II trial is studying giving paclitaxel and carboplatin together with bevacizumab to see how well it works when given with or without cixutumumab in treating patients with stage IV or recurrent non-small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: bevacizumab
Biological: cixutumumab
Drug: carboplatin
Drug: paclitaxel
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-Squamous Non- Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 180
Study Start Date: June 2009
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Biological: bevacizumab
Given IV
Drug: carboplatin
Given IV
Drug: paclitaxel
Given IV
Arm II: Experimental
Patients receive paclitaxel, carboplatin, and bevacizumab as in arm I. Patients also receive cixutumumab IV over 1 hour on days 1, 8, and 15.
Biological: bevacizumab
Given IV
Biological: cixutumumab
Given IV
Drug: carboplatin
Given IV
Drug: paclitaxel
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the progression-free survival with the combination of carboplatin, paclitaxel, and bevacizumab with vs without cixutumumab in patients with stage IV or recurrent non-squamous, non-small cell lung cancer.

Secondary

  • To evaluate overall survival of and response rate in these patients treated with these regimens.
  • To evaluate the toxicities of the above regimens in these patients.
  • To evaluate correlatives related to IGF-1R/IGF and VEGF signaling in blood samples and archival tumor specimens.

OUTLINE: Patients are stratified according to ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
  • Arm II: Patients receive paclitaxel, carboplatin, and bevacizumab as in arm I. Patients also receive cixutumumab IV over 1 hour on days 1, 8, and 15. In both arms, treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with bevacizumab and cixutumumab may continue in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed non-squamous, non-small cell lung cancer (NSCLC), including any of the following subtypes*:

    • Adenocarcinoma
    • Large cell
    • Bronchioloalveolar
    • NSCLC not otherwise specified NOTE: *Mixed tumors will be categorized by the predominant cell type unless small cell or squamous cell elements are present, in which case the patient is ineligible
  • Advanced disease, as defined by any of the following:

    • Stage IV (M1a or M1b)* disease based on the TNM staging system
    • Recurrent disease after prior radiotherapy or surgery NOTE: *In the current revision of the AJCC staging system (v7, 2009), former stage IIIB with malignant pleural effusion will now be classified as Stage IV (M1a).
  • Measurable disease, as defined by RECIST (PET and the PET portion of PET/CT are not acceptable methods of evaluation for response)

    • No prior radiotherapy to the only area of measurable disease unless there is progression of disease documented by physical examination, imaging tests, or pathology in this region
  • Brain metastases are allowed, provided they have been treated with surgery and/or radiotherapy, the patient is neurologically stable, and repeat brain imaging shows no progression in the brain

    • Patients must undergo head CT scan or MRI within 4 weeks prior to randomization for evaluation
    • At least 6 weeks since prior craniotomy and ≥ 4 weeks since prior radiotherapy

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin normal
  • Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Blood glucose normal (fasting < 120 mg/dL or below ULN)
  • AST and ALT ≤ 3 times ULN
  • Alkaline phosphatase ≤ 3 times ULN
  • Urine protein by dipstick ≤ 1+ (within 2 weeks of randomization) OR urine protein:creatinine < 1.0
  • INR < 1.5 or PTT normal
  • Neuropathy ≤ CTCAE grade 1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No prior allergic reaction to compounds of chemical or biological composition similar to those of cixutumumab
  • No known hypersensitivity to any component of bevacizumab
  • No poorly controlled diabetes mellitus

    • History of diabetes mellitus allowed, provided blood glucose is within normal range
  • No history of other invasive malignancies unless there is no active disease and all treatment has been completed > 3 years prior to study

    • Patients with history of in-situ malignancies and curatively resected nonmelanomatous skin cancer are allowed
  • No history of thrombotic or hemorrhagic disorders
  • No history of bleeding diathesis or coagulopathy
  • No bleeding ≥ grade 2 (CTCAE version 3) requiring intervention within the past 4 weeks
  • No history of gross hemoptysis (defined as > ½ teaspoon of bright red blood)
  • No history of hypertensive crisis or hypertensive encephalopathy
  • History of hypertension allowed provided it is well-controlled (< 150/90 mm Hg) by stable anti-hypertensive therapy
  • None of the following conditions within the past 6 months:

    • Abdominal fistula
    • Gastrointestinal perforation
    • Intra-abdominal abscess
    • Myocardial infarction
    • Stroke
    • Any CNS cerebrovascular ischemia
    • New York Heart Association class II-IV congestive heart failure or severe heart failure
    • Unstable or symptomatic angina pectoris
    • Significant vascular disease
    • Symptomatic peripheral vascular disease
  • No ongoing, serious cardiac arrhythmia requiring medication
  • No ongoing, active infection or fever
  • No co-existing medical condition, psychiatric illness or limitations that would interfere with compliance of study requirements
  • No serious non-healing wound, ulcer, bone fracture within the past 4 weeks

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy or biologic or molecular targeted therapy for advanced NSCLC
  • No prior cixutumumab or another IGF-IR inhibitor
  • At least 3 weeks since prior radiotherapy and recovered
  • More than 1 year since prior chemotherapy and/or biological or molecular targeted therapy as part of initial potentially curative therapy (i.e., one regimen of induction and/or adjuvant and/or concurrent chemoradiotherapy)
  • More than 4 weeks since prior and no concurrent major surgical procedure
  • More than 7 days since prior minor surgical procedure
  • More than 1 week since prior and no concurrent daily treatment with acetylsalicylic acid (> 325 mg/day) or non-steroidal anti-inflammatory agents
  • More than 1 week since prior and no concurrent dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal)
  • No concurrent therapeutic anticoagulation, except prophylactic anticoagulation of venous access device
  • No concurrent combination antiretroviral therapy in HIV-positive patients
  • No other concurrent anticancer therapy (e.g., biologic agents, chemotherapy, or radiotherapy)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00955305

Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Athanassios Argiris, MD UPMC Cancer Centers
  More Information

Additional Information:
No publications provided

Responsible Party: ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers: CDR0000651469, ECOG-E3508
Study First Received: August 7, 2009
Last Updated: September 4, 2009
ClinicalTrials.gov Identifier: NCT00955305     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer

Study placed in the following topic categories:
Thoracic Neoplasms
Adenocarcinoma, Bronchiolo-Alveolar
Antimitotic Agents
Carboplatin
Bevacizumab
Angiogenesis Inhibitors
Recurrence
Carcinoma
Respiratory Tract Diseases
Lung Neoplasms
Paclitaxel
Lung Diseases
Tubulin Modulators
Non-small Cell Lung Cancer
Adenocarcinoma of Lung
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Thoracic Neoplasms
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Growth Substances
Mitosis Modulators
Carboplatin
Antimitotic Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Carcinoma
Neoplasms
Paclitaxel
Lung Diseases
Tubulin Modulators
Carcinoma, Non-Small-Cell Lung
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009