Phase 2 Trial of Bevacizumab in Combination With Pemetrexed

NCT ID: NCT00227019

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2016-12-31

Brief Summary

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).

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

Conditions

Non-small Cell Lung Cancer (NSCLC); Lung Cancer; Neoplasm Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bevacizumab+ pemetrexed

pemetrexed (500 mg/m² IV) + bevacizumab (15 mg/kg IV). In addition to Vitamin B12 + Folate + Dexamethasone

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

15 mg/kg, IV over 10 minutes every 3 weeks

Pemetrexed

Intervention Type: DRUG

500 mg/m²; IV over 10 minutes every 3 weeks

Vitamin B12

Intervention Type: DRUG

1000 micrograms, IM injection 1-2 weeks prior to treatment and repeated every 9 weeks until last dose of pemetrexed

Folate

Intervention Type: DRUG

350 to 1000 micrograms 1 week prior to treatment and 3 weeks after last pemetrexed dose

Dexamethasone

Intervention Type: DRUG

4 mg; oral, twice a day at the following times: the day before, of and after each dose of pemetrexed

Interventions

Bevacizumab

15 mg/kg, IV over 10 minutes every 3 weeks

Intervention Type: DRUG

Pemetrexed

500 mg/m²; IV over 10 minutes every 3 weeks

Intervention Type: DRUG

Vitamin B12

1000 micrograms, IM injection 1-2 weeks prior to treatment and repeated every 9 weeks until last dose of pemetrexed

Intervention Type: DRUG

Folate

350 to 1000 micrograms 1 week prior to treatment and 3 weeks after last pemetrexed dose

Intervention Type: DRUG

Dexamethasone

4 mg; oral, twice a day at the following times: the day before, of and after each dose of pemetrexed

Intervention Type: DRUG

Other Intervention Names

Avastin; Alimta; cobalamin; Vit B12; folacin; Folic acid; pteroyl-L-glutamic acid; pteroyl-L-glutamate; pteroylmonoglutamic acid; vitamin B9; vitamin Bc; Decadron

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Heather Wakelee

OTHER

Sponsor Role: lead

Responsible Party

Heather Wakelee

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Heather A. Wakelee

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Cooper Cancer Institute

Voorhees Township, New Jersey, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

95913

Identifier Type: OTHER

Identifier Source: secondary_id

LUN0014

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-00892

Identifier Type: -

Identifier Source: org_study_id