Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent 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:
NCT00955305
First received: August 7, 2009
Last updated: April 9, 2014
Last verified: April 2014
  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. 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.


Condition Intervention Phase
Adenocarcinoma of the Lung
Bronchoalveolar Cell Lung Cancer
Large Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Biological: cixutumumab
Drug: paclitaxel
Drug: carboplatin
Biological: bevacizumab
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: 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 assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: From randomization to disease progression or death from any cause, up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and compared by the stratified log-rank test.

  • Response rate (CR+PR) assessed by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to compare the response rates.

  • Incidence of toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.


Estimated Enrollment: 180
Study Start Date: March 2010
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Experimental: Arm II (cixutumumab, paclitaxel, carboplatin, bevacizumab)
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: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Detailed Description:

PRIMARY OBJECTIVES:

I. 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 OBJECTIVES:

I. To evaluate overall survival and response rate of the above combination in patients with non-squamous, advanced non-small cell lung cancer.

II. To evaluate the toxicities of the above combination in patients with non-squamous advanced non-small cell lung cancer.

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 intravenously (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

Inclusion Criteria:

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

    • Adenocarcinoma
    • Large cell
    • Bronchioloalveolar
    • NSCLC not otherwise specified
  • 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
  • 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 tumor 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
  • 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)
  • Fasting 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
    • Patients with a history of breast cancer (without evidence of disease for ≥ 3 years) who recently completed adjuvant hormonal therapy < 3 years from the date of registration are eligible
  • 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 4weeks
  • 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
  • No other concurrent anticancer therapy (e.g., biologic agents, chemotherapy, or radiotherapy)
  • 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 other non-steroidalanti-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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00955305

  Show 165 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Athanassios (Ethan) Argiris Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00955305     History of Changes
Other Study ID Numbers: NCI-2011-01960, NCI-2011-01960, CDR0000651469, ECOG-E3508, E3508, E3508, U10CA021115
Study First Received: August 7, 2009
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Adenocarcinoma, Bronchiolo-Alveolar
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antibodies
Antibodies, Monoclonal
Bevacizumab
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