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Phase 2 Trial of Bevacizumab in Combination With Pemetrexed

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00227019
First Posted: September 27, 2005
Last Update Posted: March 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Eli Lilly and Company
Genentech, Inc.
Information provided by (Responsible Party):
Heather Wakelee, Stanford University
  Purpose
This trial evaluated the safety of combining bevacizumab and pemetrexed in non-small cell lung cancer (NSCLC) patients with stable brain metastases as second-line chemotherapy, while evaluating progression-free survival (PFS) and overall survival (OS).

Condition Intervention Phase
Non-small Cell Lung Cancer (NSCLC) Lung Cancer Neoplasm Metastasis Drug: Bevacizumab Drug: Pemetrexed Drug: Vitamin B12 Drug: Folate Drug: Dexamethasone Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Bevacizumab in Combination With Pemetrexed as Second Line Therapy in Patients With Stable Brain Metastases From Non-small Cell Lung Cancer (NSCLC) (Excluding Squamous Cell Carcinoma)

Resource links provided by NLM:


Further study details as provided by Heather Wakelee, Stanford University:

Primary Outcome Measures:
  • Incidence of Central Nervous System (CNS) Hemorrhagic Events [ Time Frame: 18 months ]
    Number of events of brain or central nervous system (CNS) bleeding


Secondary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: 18 months ]

    Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of documented disease progression or death.

    Kaplan-Meier survival curves for PFS were generated with IBM SPSS Statistics version 19.0 (SPSS, Inc, Chicago, IL).


  • Overall Survival (OS) [ Time Frame: 18 months ]

    Overall Survival (OS) is defined as the duration of time from start of treatment to deat.

    Kaplan-Meier survival curves for OS were generated with IBM SPSS Statistics version 19.0 (SPSS, Inc, Chicago, IL).



Enrollment: 16
Study Start Date: March 2006
Study Completion Date: December 2016
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bevacizumab+ pemetrexed
pemetrexed (500 mg/m² IV) + bevacizumab (15 mg/kg IV). In addition to Vitamin B12 + Folate + Dexamethasone
Drug: Bevacizumab
15 mg/kg, IV over 10 minutes every 3 weeks
Other Name: Avastin
Drug: Pemetrexed
500 mg/m²; IV over 10 minutes every 3 weeks
Other Name: Alimta
Drug: Vitamin B12
1000 micrograms, IM injection 1-2 weeks prior to treatment and repeated every 9 weeks until last dose of pemetrexed
Other Names:
  • cobalamin
  • Vit B12
Drug: Folate
350 to 1000 micrograms 1 week prior to treatment and 3 weeks after last pemetrexed dose
Other Names:
  • folacin
  • Folic acid
  • pteroyl-L-glutamic acid
  • pteroyl-L-glutamate
  • pteroylmonoglutamic acid
  • vitamin B9
  • vitamin Bc
Drug: Dexamethasone
4 mg; oral, twice a day at the following times: the day before, of and after each dose of pemetrexed
Other Name: Decadron

Detailed Description:

Brain metastases are a common complication of advanced non-small-cell lung cancer (NSCLC) both at initial presentation and at the time of disease progression. Patients with brain metastases have often been excluded from large randomized phase III trials due to concerns of poorer survival and impaired ability of drugs to cross the blood-brain barrier. However, as survival has improved, some trials have included such patients, often finding similar benefit to patients with metastatic disease elsewhere.

Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor, has emerged as an important adjunct to platinum-based chemotherapy doublets for use in advanced NSCLC. This drug is normally used as a first line chemotherapy. Pemetrexed is a multi-targeted anti-folate agent,which is approved for use in first-line (with platinum), maintenance, and second-line treatment of advanced nonsquamous NSCLC. Based on the efficacy of pemetrexed as a second line agent and the safety questions surrounding bevacizumab in those with treated brain metastases, a trial was designed to look at the combination of both agents as a second line therapy in NSCLC patients with treated stable brain metastases

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced stage NSCLC excluding squamous cell histology with measurable or evaluable disease.
  • Stable brain metastases required, no longer requiring active therapy such as steroid medications, which have been previously treated with radiation or surgery or both and have been documented to be stable on repeat imaging done at least one month after completion of therapy.
  • Prior therapy with one standard doublet front-line regimen for NSCLC (platinum containing)
  • Life expectancy of at least 3 months
  • ECOG Performance status 0-1
  • Age 18 or higher
  • Use of effective means of contraception (men and women) in subjects of child-bearing potential
  • Ability/willingness to comply with vitamin supplementation including vitamin B 12 and folic acid started at least 1 week before first dose of pemetrexed and continued for at least 3 weeks after last dose
  • Ability/willingness to take dexamethasone the day before, of and after pemetrexed administration
  • Drainage of any clinically significant effusion
  • Ability to sign informed consent

Exclusion Criteria:

  • Treatment with more than one prior chemotherapy regimen (unless one regimen was stopped for toxicity reasons with a different regimen replacement regimen started immediately and patient completed only 4-6 total cycles of first-line treatment. One prior regimen (up to 4 cycles) of neoadjuvant or adjuvant therapy for early stage disease will also be allowed.
  • Prior treatment with pemetrexed or bevacizumab
  • Prior chemotherapy within 28 days (6 weeks for BCNU, CCNU or mitomycin-C)
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in any other experimental drug study
  • Concomitant chemotherapy, radiotherapy or investigational agents
  • Uncontrolled effusion (large pleural or peritoneal effusion or small/moderate effusion which requires drainage for symptom management)
  • Evidence of bleeding diathesis or coagulopathy
  • Use of anti-coagulant agents including warfarin, heparin, aspirin, NSAIDs
  • Pregnant (positive pregnancy test) or lactating women
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
  • Urine protein:creatinine ratio greater than or equal to 1.0 at screening
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
  • Serious, non-healing wound, ulcer, or bone fracture
  • Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, or with significant cavitation as assessed by treating investigator in consultation with an attending radiologist
  • History of hemoptysis (bright red blood of 1/2 teaspoon or more)
  • Neutrophils < 1.5 x 10^9/ L
  • Hemoglobin <10.0 g/dl
  • Platelets <100 x 10^9/ L
  • Serum glutamic oxaloacetic transaminase (SGOT/ AST) or serum glutamic pyruvic transaminase (SGPT/ ALT) > 2.5 times upper limits of normal
  • Creatinine > 1.5 times upper limits of normal
  • Significant co-morbidities including:

    • Blood pressure of greater than 150/100 mmHg
    • Unstable angina
    • New York Heart Association (NYHA) Grade II or greater congestive heart failure
    • History of myocardial infarction within 6 months
    • History of stroke within 6 months
    • Clinically significant peripheral vascular disease
  • Inability to comply with study and/or follow-up procedures
  Contacts and Locations
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): NCT00227019


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, New Hampshire
Norris Cotton Cancer Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Cooper Cancer Institute
Voorhees, New Jersey, United States, 08043
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Heather Wakelee
Eli Lilly and Company
Genentech, Inc.
Investigators
Principal Investigator: Heather A. Wakelee Stanford University
  More Information

Responsible Party: Heather Wakelee, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00227019     History of Changes
Other Study ID Numbers: IRB-00892
95913 ( Other Identifier: Stanford University Alternate IRB Approval Number )
LUN0014 ( Other Identifier: OnCore )
First Submitted: September 8, 2005
First Posted: September 27, 2005
Results First Submitted: April 20, 2016
Last Update Posted: March 6, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasm Metastasis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Vitamins
Vitamin B 12
Hydroxocobalamin
Folic Acid
Dexamethasone acetate
Dexamethasone
Bevacizumab
Pemetrexed
BB 1101
Vitamin B Complex
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents