Phase II Trial of Bevacizumab in Combination With Pemetrexed as 2nd Line Therapy in Patients With Stable Brain Metastases From Non-small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Eli Lilly and Company
Genentech
Information provided by (Responsible Party):
Heather Wakelee, Stanford University
ClinicalTrials.gov Identifier:
NCT00227019
First received: September 8, 2005
Last updated: August 6, 2013
Last verified: August 2013
  Purpose

This study seeks to evaluate the safety of combining bevacizumab and pemetrexed in non-small cell lung cancer (NSCLC) patients with stable brain metastases as second line chemotherapy, while also looking for an improvement in progression free survival (PFS) as well as overall survival.


Condition Intervention Phase
Neoplasm Metastasis
Lung Cancer
Drug: Bevacizumab
Drug: Pemetrexed
Drug: Vitamin B12
Drug: folate
Drug: dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Stanford University:

Primary Outcome Measures:
  • Safety of combining bevacizumab and pemetrexed in non-small cell lung cancer (NSCLC) patients with stable brain metastases [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • Progression free survival (PFS) and overall survival [ Time Frame: unknown ] [ Designated as safety issue: No ]
    18 months

  • tumor contamination [ Time Frame: unknown ] [ Designated as safety issue: No ]
    18 months


Estimated Enrollment: 40
Study Start Date: March 2006
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bevacizumab + pemetrexed Drug: Bevacizumab
15 mg/kg
Other Name: Avastin
Drug: Pemetrexed
500mg/m2; IV over 10 minutes every 3 weeks
Other Name: Alimta
Drug: Vitamin B12
1000 micrograms
Other Names:
  • cobalamin
  • vitamin B-12
Drug: folate
350-1000 micrograms
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:

The purpose of this study is to evaluate the safety of combining bevacizumab and pemetrexed in non-small cell lung cancer (NSCLC) patients with stable brain metastases as second line chemotherapy, while also looking for an improvement in progression free survival (PFS) and overall survival. Bevacizumab has proven efficacy in improving survival when combined with chemotherapy for the treatment of colon cancer and shows great promise for the treatment of other malignancies including NSCLC.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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)
  • 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
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: 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
Investigators
Principal Investigator: Heather A. Wakelee Stanford University
  More Information

No publications provided

Responsible Party: Heather Wakelee, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00227019     History of Changes
Other Study ID Numbers: LUN0014, 95913
Study First Received: September 8, 2005
Last Updated: August 6, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Lung Neoplasms
Neoplasm Metastasis
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplastic Processes
Pathologic Processes
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Pemetrexed
Bevacizumab
BB 1101
Folic Acid
Vitamin B Complex
Vitamin B 12
Hydroxocobalamin
Vitamins
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 22, 2014