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: July 22, 2014
Last verified: May 2014
  Purpose

This randomized phase II trial studies how well paclitaxel, carboplatin and bevacizumab 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, by stopping them from dividing, or by stopping them from spreading. 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, defined as the proportion of patients with complete response or partial response, evaluated using RECIST criteria [ 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 toxicities, graded using the revised National Cancer Institute CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

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, and +/- IMC-A12 (cixutumumab) in patients with advanced, 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 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:

  • Patients must have histologically or cytologically confirmed non-squamous, non-small cell lung cancer (NSCLC); the following histological subtypes will be eligible: adenocarcinoma, large cell, bronchioloalveolar, and NSCLC not otherwise specified; 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; cytologic or histologic diagnosis can be established on metastatic tumor aspirates or biopsy; squamous cell carcinomas will be excluded
  • Patients must have advanced NSCLC defined as either:

    • Recurrent disease after prior radiation or surgery
    • Stage IV (M1a or M1b) based on the TNM staging system (American Joint Committee on Cancer [AJCC] 2009)
    • 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)
  • Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST); baseline measurements/evaluations of all sites of disease (of target and non-target disease sites) must be obtained within 4 weeks prior to randomization

    • NOTE: Positron emission tomography (PET) and PET portion of PET/computed tomography (CT) are not acceptable methods of evaluation for response
    • NOTE: For lesions located in a previously irradiated area to be considered measurable disease, criteria must be met
    • NOTE: No prior radiation therapy to the only area of measurable disease unless there is documented progression of disease documented by physical examination, imaging tests, or pathology in this region
  • No prior chemotherapy or biologic/molecular targeted therapy for advanced NSCLC; prior chemotherapy and/or biological/molecular targeted therapy as part of initial potentially curative therapy (one regimen of induction and/or adjuvant and/or concurrent chemoradiotherapy) is allowed provided it has been completed 1 year or more prior to randomization
  • No prior treatment with IMC-A12 or another insulin-like growth factor 1 receptor (IGF-IR) inhibitor
  • Prior radiation therapy is allowed if it has been completed 3 weeks prior to randomization and patient has recovered from any adverse events related to radiation therapy (RT)
  • A head CT or magnetic resonance imaging (MRI) is required within 4 weeks prior to randomization for evaluation
  • 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; at least 6 weeks should have elapsed from the time of craniotomy and at least 4 weeks from radiotherapy; NOTE: Repeat MRI or CT scan should show stability or improvement in the metastatic brain lesions; patients should be neurologically stable and, if on corticosteroids, be on stable or decreasing doses of corticosteroids
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 only
  • Absolute neutrophil count (ANC) >= 1500/mm³
  • Platelet count >= 100,000/mm³
  • Total bilirubin within institutional upper limit of normal (ULN)
  • Serum creatinine =< 1.5 x ULN
  • Fasting blood glucose within normal range (fasting < 120 mg/dL or below ULN)
  • Alkaline phosphatase (ALP) =< 3 x ULN
  • Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3 x ULN
  • Urine dipstick must be =< 0-1+ within 2 weeks (14 days) of randomization; if urine dipstick result is > 1+, a calculation of urine protein creatinine (UPC) ratio is required; patients must have a UPC ratio < 1.0 to participate in the study
  • Patients must not be on therapeutic anticoagulation; patients international normalized ratio (INR) must be =< 1.5 or partial thromboplastin time (PTT) =< upper limits of normal within 2 weeks prior to randomization; prophylactic anticoagulation of venous access devices is allowed provided the criteria have been met; caution should be taken when treating patients with low dose heparin or low molecular weight heparin for deep vein thrombosis (DVT) prophylaxis during treatment with bevacizumab, as there may be an increased risk of bleeding
  • Neuropathy, if present at baseline, must be =< Common Terminology Criteria for Adverse Events (CTCAE) grade 1
  • No prior allergic reaction to compounds of chemical or biologic composition similar to those of IMC-A12; no known hypersensitivity to any component of bevacizumab
  • Patients with poorly controlled diabetes mellitus are excluded; patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN)
  • No history of other invasive malignancies unless there is no active disease and all treatment has been completed >= 3 years prior to randomization; patients with history of in-situ malignancies and curatively resected nonmelanomatous skin cancer are eligible

    • NOTE: 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
  • Patient must have no history of thrombotic or hemorrhagic disorders; patients must have no history of bleeding diathesis or coagulopathy
  • Patients must not have >= grade 2 bleeding or any bleeding requiring intervention within 4 weeks prior to randomization (please see the Cancer Therapy Evaluation Program [CTEP] active version of the CTCAE)
  • Patients with a history of hypertension must be well-controlled (=< 150/90) on a stable regimen of anti-hypertensive therapy
  • Patients must have no history of gross hemoptysis (defined as >= 1/2 teaspoon of bright red blood)
  • Patients must not have had any of the following within 6 months prior to randomization:

    • Abdominal fistula
    • Gastrointestinal perforation
    • Intra-abdominal abscess
    • Previous myocardial infarction
    • History of any central nervous system (CNS) cerebrovascular ischemia
    • New York Heart Association (NYHA) > class II congestive heart failure or severe heart failure
    • Unstable or symptomatic angina pectoris
    • History of stroke
    • Significant vascular disease
    • Symptomatic peripheral vascular disease
  • Patients must not have an ongoing, serious cardiac arrhythmia requiring medication at time of randomization
  • Patients must not have ongoing, active infection or ongoing fever at the time of randomization or have any co-existing medical condition, psychiatric illness or limitations that would interfere with compliance of study requirements
  • Patients must not have a history of hypertensive crisis or hypertensive encephalopathy
  • Patients must not have had any of the following within 4 weeks prior to randomization: a serious non-healing wound, ulcer, bone fracture, or major surgical procedure

    • NOTE: Patients must not have received minor surgery within 7 days prior to randomization
  • Patient must not have any anticipated major surgical procedure(s) during the course of the study
  • Patients must not be receiving daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents (NSAIDs) known to inhibit platelet function for chronic conditions; patients must not be receiving treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal); if patient was receiving any of the following: aspirin (> 325 mg/day), NSAID, and/or anti-platelet drugs, patient must have discontinued its use >= 1 week prior to randomization
  • Female participants must not be pregnant or breast-feeding; women of childbearing potential must have a negative pregnancy test; all females of childbearing potential must have a blood test within 1 week prior to randomization to rule out pregnancy
  • Women of childbearing potential and sexually active males should use an accepted and effective method of contraception while on treatment and for 3 months thereafter
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are not eligible
  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: NCT00955305

  Show 166 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Athanassios (Ethan) Argiris ECOG-ACRIN Cancer Research 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, U10CA180820, U10CA021115
Study First Received: August 7, 2009
Last Updated: July 22, 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 July 22, 2014