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Pemetrexed Disodium, Gemcitabine, and Bevacizumab in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: February 20, 2007   Last Updated: June 9, 2009   History of Changes
Sponsors and Collaborators: Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00438204
  Purpose

RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, 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, 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 pemetrexed disodium and gemcitabine together with bevacizumab may kill more tumor cells.

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


Condition Intervention Phase
Lung Cancer
Biological: bevacizumab
Drug: gemcitabine hydrochloride
Drug: pemetrexed disodium
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Trial of Pemetrexed, Gemcitabine, and Bevacizumab Every Two Weeks in Chemotherapy-Naive Patients With Stages IIIB/IV Non- Squamous, Non-Small Cell Lung Cancer (NSCLC)

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:
  • Response rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: May 2006
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the efficacy of pemetrexed disodium, gemcitabine hydrochloride, and bevacizumab in chemotherapy-naïve patients with stage IIIB or IV nonsquamous cell non-small cell lung cancer.

Secondary

  • Determine the response rate in patients treated with this regimen.
  • Determine the time to treatment failure in patients treated with this regimen.
  • Determine the overall survival of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes, gemcitabine hydrochloride IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients may then receive bevacizumab alone in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed periodically for 6 months.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

  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 nonsquamous cell non-small cell lung cancer (NSCLC), including the following cell types:

    • Adenocarcinoma
    • Bronchoalveolar
    • Large cell carcinoma
  • Stage IIIB or IV NSCLC

    • Patients with stage IIIB disease must have a pleural effusion OR not be a candidate for chemoradiotherapy as treatment for locally advanced disease
  • Unidimensionally measurable or evaluable disease

    • Disease in a prior radiation port must have documented progression
  • No tumor with cavitation or close proximity to a major vessel
  • No CNS or untreated brain metastases

    • Treated brain metastases allowed provided there is no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as determined by clinical examination and brain imaging (MRI or CT) during the screening period

      • Treatment for brain metastases may include whole brain radiotherapy, radiosurgery (i.e., Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician
      • Stable-dose anticonvulsants allowed
    • Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 are not allowed
  • No clinically significant effusion that cannot be drained
  • No disease that cannot be radiologically imaged

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy > 12 weeks
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin > 8 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
  • AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement)
  • Creatinine clearance ≥ 45 mL/min
  • Urine protein:creatinine ratio ≤ 1.0
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No significant cardiovascular illness, including any of the following:

    • Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg)
    • Myocardial infarction within the past 6 months
    • Unstable angina
    • Hemorrhagic or thrombotic stroke or other CNS bleeding within the past 6 months
    • Clinically significant peripheral vascular disease
    • Evidence of bleeding diathesis or coagulopathy
    • New York Heart Association class II-IV congestive heart failure
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No significant traumatic injury within the past 28 days
  • No serious, nonhealing wound, ulcer, or bone fracture
  • No hemoptysis > grade 2 within the past 28 days
  • No hematemesis > grade 2 within the past 6 months OR grade 1 hematemesis within the past 28 days
  • No inability to take dexamethasone, folic acid, or cyanocobalamin (vitamin B12)
  • No other serious systemic disorder (including oncologic emergencies) incompatible with study treatment
  • No other malignancy within the past 3 years except for adequately treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 1 week since prior minor surgical procedure, such as fine-needle aspiration or core biopsy
  • At least 4 weeks since prior and no concurrent major surgery or open biopsy
  • At least 4 weeks since prior radiotherapy
  • At least 4 weeks since prior and no concurrent participation in another experimental drug study other than a Genentech-sponsored bevacizumab cancer study
  • No prior chemotherapy
  • No concurrent stimulators of thrombopoiesis
  • No concurrent full-dose anticoagulants
  • No nonsteroidal anti-inflammatory drugs (NSAIDs) 2 days before, during, and 2 days after pemetrexed disodium administration (5 days before for NSAIDs [including cyclooxygenase-2 inhibitors] with a long half-life [e.g., naproxen, piroxicam, diflunisal, nabumetone, rofecoxib, or celecoxib])
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00438204

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute     313-576-9363        
University of Michigan Comprehensive Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109-0942
Contact: Clinical Trials Office - University of Michigan Comprehensive     800-865-1125        
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Antoinette J. Wozniak, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Barbara Ann Karmanos Cancer Institute ( Antoinette J. Wozniak )
Study ID Numbers: CDR0000531832, WSU-2005-008, WSU-036806MP4F
Study First Received: February 20, 2007
Last Updated: June 9, 2009
ClinicalTrials.gov Identifier: NCT00438204     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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
recurrent non-small cell lung cancer

Study placed in the following topic categories:
Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Immunologic Factors
Folate
Bevacizumab
Vitamin B9
Respiratory Tract Diseases
Lung Neoplasms
Gemcitabine
Adenocarcinoma, Bronchiolo-Alveolar
Folic Acid Antagonists
Folinic Acid
Antiviral Agents
Immunosuppressive Agents
Angiogenesis Inhibitors
Recurrence
Carcinoma
Pemetrexed
Folic Acid
Radiation-Sensitizing Agents
Lung Diseases
Non-small Cell Lung Cancer
Adenocarcinoma of Lung
Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Bevacizumab
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Gemcitabine
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Growth Substances
Enzyme Inhibitors
Folic Acid Antagonists
Angiogenesis Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Pemetrexed
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases

ClinicalTrials.gov processed this record on September 10, 2009