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

Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00227019
• Other study ID #: LUN0014
• Secondary ID: 95913
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 8, 2005
• Last updated: April 21, 2015
• Start date: March 2006
• Est. completion date: December 2015

Study information

• Verified date: April 2015
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Neoplasm Metastasis

Intervention

Drug:
• Bevacizumab
15 mg/kg
• Pemetrexed
500mg/m2; IV over 10 minutes every 3 weeks
• Vitamin B12
1000 micrograms
• folate
350-1000 micrograms
• dexamethasone
4 mg; oral, twice a day at the following times: the day before, of and after each dose of pemetrexed

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Stanford University School of Medicine	Stanford	California
United States	Cooper Cancer Institute	Voorhees	New Jersey

Sponsors (3)

Lead Sponsor	Collaborator
Heather Wakelee	Eli Lilly and Company, Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of combining bevacizumab and pemetrexed in non-small cell lung cancer (NSCLC) patients with stable brain metastases		18 months	Yes
Primary	Progression free survival (PFS) and overall survival	18 months	unknown	No
Primary	tumor contamination	18 months	unknown	No