Phase 2 Trial of Bevacizumab in Combination With Pemetrexed

NCT00227019 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB-0089295913LUN0014
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Central Nervous System (CNS) Hemorrhagic Events

  Number of events of brain or central nervous system (CNS) bleeding

  18 months

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  18 months

• Overall Survival (OS)

  18 months

Study Arms (1)

bevacizumab+ pemetrexed

EXPERIMENTAL

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

Drug: Bevacizumab; Drug: Pemetrexed; Drug: Vitamin B12; Drug: Folate; Drug: Dexamethasone

Interventions

Bevacizumab DRUG

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

Also known as: Avastin

bevacizumab+ pemetrexed

Pemetrexed DRUG

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

Also known as: Alimta

bevacizumab+ pemetrexed

Vitamin B12 DRUG

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

Also known as: cobalamin, Vit B12

bevacizumab+ pemetrexed

Folate DRUG

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

Also known as: folacin, Folic acid, pteroyl-L-glutamic acid, pteroyl-L-glutamate, pteroylmonoglutamic acid, vitamin B9, vitamin Bc

bevacizumab+ pemetrexed

Dexamethasone DRUG

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

Also known as: Decadron

bevacizumab+ pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heather Wakelee: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator

Study Sites (4)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Cooper Cancer Institute

Voorhees Township, New Jersey, 08043, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoplasm Metastasis

Interventions

Bevacizumab; Pemetrexed; Vitamin B 12; Folic Acid; Leucovorin; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds; Pterins; Pteridines; Formyltetrahydrofolates; Tetrahydrofolates; Coenzymes; Enzymes and Coenzymes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Heather Wakelee, MD
• Organization: Stanford University

hwakelee@stanford.edu

650-736-7221

Study Officials

• Heather A. Wakelee

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 27, 2005
• Study Start: March 1, 2006
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2016
• Last Updated: March 6, 2017
• Results First Posted: March 6, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)