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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Antoinette J. Wozniak, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00438204
First received: February 20, 2007
Last updated: September 13, 2013
Last verified: September 2013
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Change in tumor size from baseline beginning with cycle 4 then every 4 cycles thereafter. ] [ Designated as safety issue: No ]
    Progression-free survival will be defined as the time from the first day of treatment until the date that progressive disease (PD), symptomatic deterioration, or death due to any cause is first reported. Patients who die without reported prior progression will be considered to have progressed on the day of their death. Patients who did not progress will be censored at the day of last tumor assessment.


Secondary Outcome Measures:
  • Response rate [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Every two weeks ] [ Designated as safety issue: Yes ]
  • Time to treatment failure [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 27
Study Start Date: May 2006
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab, gemcitabine hydrochloride

Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days

Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days

Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.

Biological: bevacizumab
Bevacizumab 10mg/kg IV over 90 ± 15 minutes every 14 days
Other Name: Avastin ®
Drug: gemcitabine hydrochloride
Gemcitabine 1200 mg/m2 intravenously over 30 minutes following the pemetrexed every 14 days
Other Name: Gemzar ®
Drug: pemetrexed disodium
Pemetrexed 400 mg/m2 intravenously over 10 minutes every 14 days.
Other Name: Alimta®

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
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Principal Investigator: Antoinette J. Wozniak, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Antoinette J. Wozniak, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00438204     History of Changes
Other Study ID Numbers: CDR0000531832, P30CA022453, WSU-2005-008, WSU-036806MP4F
Study First Received: February 20, 2007
Last Updated: September 13, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by Barbara Ann Karmanos Cancer Institute:
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

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

ClinicalTrials.gov processed this record on April 17, 2014