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Carboplatin, Pemetrexed Disodium, and Bevacizumab in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00234052
Recruitment Status : Completed
First Posted : October 6, 2005
Results First Posted : May 16, 2019
Last Update Posted : June 4, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as carboplatin and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving carboplatin and pemetrexed disodium together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin and pemetrexed disodium together with bevacizumab works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.


Condition or disease Intervention/treatment Phase
Lung Cancer Biological: bevacizumab Drug: carboplatin Drug: pemetrexed Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • Determine the median time to disease progression in patients with stage IIIB or IV or recurrent non-squamous cell non-small cell lung cancer treated with carboplatin, pemetrexed disodium, and bevacizumab.

Secondary

  • Determine the response rate and duration of response in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.
  • Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive pemetrexed disodium IV over 10 minutes, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, patients with complete response, partial response, or stable disease continue to receive pemetrexed disodium and bevacizumab in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
Actual Study Start Date : July 28, 2005
Actual Primary Completion Date : March 1, 2011
Actual Study Completion Date : November 28, 2011


Arm Intervention/treatment
Experimental: Treatment Arm
Carboplatin + pemetrexed + bevacizumab
Biological: bevacizumab
5 mg/kg administered intravenously over 90 minutes on day 1 of each cycle (cycle = 3 weeks)
Other Name: Avastin

Drug: carboplatin
Administered intravenously at a dose of AUC=6 over 30 minutes on day 1 of each cycle (1 cycle = 3 weeks)

Drug: pemetrexed
Administered intravenously at a dose of 500 mg/m2 over 10 minutes on day 1 of each cycle (1 cycle = 3 weeks)
Other Name: pemetrexed disodium




Primary Outcome Measures :
  1. Median Progression Free Survival [ Time Frame: Approximately every 3 weeks until disease progression or death. Median follow up of 13 months (range 0.8 to 34.4 months) ]
    Progression Free Survival (PFS) in patients treated with the combination of carboplatin, pemetrexed and bevacizumab is defined as the time from registration to the time of documented disease progression or death from any cause. Patients that were lost to follow up or withdrew consent were censored at that point.


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Every two cycles until disease progression. Median follow up of 13 months (range 0.8 to 34.4 months) ]

    Overall Response Rate (ORR) of patients treated with carboplatin, pemetrexed, and bevacizumab combination is defined as the number of patients who's best response is a Complete Response (CR) plus Partial Response (PR)as recorded from the start of treatment until disease progression as assessed by RECIST 1.0.

    CR=Disappearance of all target lesions for a minimum of 4 weeks. PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions for a minimum of 4 weeks, taking as reference the baseline sum LD. No simultaneous increase in the size of any lesion or the appearance of a new lesion may occur.


  2. Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment [ Time Frame: From treatment initiation, at the beginning of each cycle where one cycle equals 21 days until 30 days post treatment (range of cycles 1-51) ]

    To characterize the toxicity profile of carboplatin, pemetrexed and bevacizumab combination treatment.

    Toxicity data will be collected from initiation of treatment, every cycle, until 30 days post last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). Only toxicity determined to be a least possibility related to at least one study drug and grade 3 or 4 was collected for this outcome measure.

    In general adverse events (AEs) will be graded according to the following:

    Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE


  3. Overall Survival Rate [ Time Frame: During treatment and then every 3 months x 2 years, then every 6 months x 3 years or until death. ]
    Overall Survival (OS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment is defined from the time of registration to the study until death from any cause. Patients that are lost to follow up will be censored from last documentation of survival status.

  4. Duration of Response [ Time Frame: From documentation of response, every two cycles (1 cycle = 21 days) until progressive disease with range of cycles completed 1-51. ]
    Duration of Response for patients treated with the combination of carboplatin, pemetrexed and bevacizumab is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date of documented progressive disease.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically* or cytologically* confirmed non-small cell lung cancer

    • Any histology, except squamous cell carcinoma, allowed

      • Mixed tumors will be categorized by the predominant cell type unless small cell elements are present, in which case the patient is ineligible
    • No histology in close proximity to a major vessel or cavitation NOTE: *Histologic or cytologic elements may be established on metastatic tumor aspirates or biopsy
  • Meets 1 of the following stage criteria:

    • Stage IIIB disease (with malignant pleural effusion)
    • Stage IV disease
    • Recurrent disease
  • Measurable or non-measurable disease
  • No known CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • No history of hemorrhagic disorders

Hepatic

  • Bilirubin < 1.5 mg/dL
  • AST and ALT < 5 times upper limit of normal
  • INR < 1.5
  • PTT normal

Renal

  • Creatinine clearance ≥ 45 mL/min
  • Urine protein:creatinine ≤ 1.0 by spot urinalysis

Cardiovascular

  • No myocardial infarction within the past 6 months
  • No New York Heart Association class II-IV congestive heart failure
  • No unstable angina pectoris
  • No serious cardiac arrhythmia requiring medication
  • No stroke within the past 6 months
  • No peripheral vascular disease ≥ grade 2
  • No uncontrolled hypertension (i.e., blood pressure ≥ 150/100 mm Hg)

    • Patients with a history of hypertension allowed provided blood pressure is well controlled on a stable regimen of anti-hypertensive therapy
  • No history of thrombotic disorders
  • No other clinically significant cardiovascular disease

Pulmonary

  • No history of gross hemoptysis, defined as bright red blood of a ½ teaspoon or more

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Must be willing and able to take daily oral folic acid, intermittent vitamin B_12 injections, and corticosteroid premedication
  • No ongoing or active infection
  • No serious, non-healing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 3 weeks since prior immunotherapy

Chemotherapy

  • No prior systemic chemotherapy

Endocrine therapy

  • More than 3 weeks since prior hormonal therapy

Radiotherapy

  • See Disease Characteristics
  • More than 3 weeks since prior radiotherapy

Surgery

  • More than 4 weeks since prior major surgery
  • More than 1 week since prior minor surgery, fine needle aspiration, or core biopsy
  • No concurrent major surgery

Other

  • Recovered from all prior therapy
  • More than 4 weeks since prior and no concurrent participation in another experimental drug study
  • No aspirin or other nonsteroidal anti-inflammatory drug (NSAID) 2 days before and 2 days after each pemetrexed disodium infusion (5 days before and 2 days after each pemetrexed disodium infusion for NSAIDs with a long half-life [e.g., naproxen, rofecoxib, or celecoxib])
  • No concurrent therapeutic anticoagulation

    • Concurrent prophylactic anticoagulation for venous access devices allowed provided requirements for INR and PTT are met
  • No concurrent administration of any of the following:

    • Chronic daily treatment with aspirin (> 325 mg per day)
    • NSAIDs known to inhibit platelet function, including any of the following:

      • Dipyridamole
      • Ticlopidine
      • Clopidogrel
      • Cilostazol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00234052


Locations
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United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Rush Cancer Institute at Rush University Medical Center
Chicago, Illinois, United States, 60612
Evanston Northwestern Healthcare - Evanston Hospital
Evanston, Illinois, United States, 60201-1781
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Advocate Lutheran General Cancer Care Center
Park Ridge, Illinois, United States, 60068-1174
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
Investigators
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Study Chair: Jyoti D. Patel Robert H. Lurie Cancer Center

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Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00234052     History of Changes
Other Study ID Numbers: NU 04L2
NU-04L2
STU00007415 ( Other Identifier: Northwestern University IRB# )
First Posted: October 6, 2005    Key Record Dates
Results First Posted: May 16, 2019
Last Update Posted: June 4, 2019
Last Verified: January 2019
Keywords provided by Northwestern University:
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer
large cell lung cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Bevacizumab
Carboplatin
Pemetrexed
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors