Bevacizumab and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme

NCT00590681 | Completed Phase 2 Results DMC

• 1 other identifier: 15149A
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 5

Brief Summary

This study is being conducted to help determine whether the addition of Avastin (an anti-cancer drug), when given along with temozolomide during the monthly cycles that follow radiation, is able to delay tumor growth, shrink tumors, or impact how long people with GBM live. This study is sponsored by Genentech, Inc., the manufacturer of Avastin. Avastin is the experimental drug being administered in this research study. Avastin binds a protein called vascular endothelial growth factor, or VEGF. VEGF is produced by tumors and circulates in the blood. One of VEGF's main roles is to support the growth of new blood vessels. During cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells and help them grow. Avastin binds to VEGF, which then prevents VEGF from functioning. In laboratory studies, Avastin prevented the growth of several different types of cancer cells grown in animals. Avastin was approved by the Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer in combination with chemotherapy. Avastin has not been approved by the FDA for the treatment of GBM and is, therefore, considered experimental. Avastin is currently undergoing testing (alone and in combination with another anti-cancer drug, irinotecan) in persons with GBM that have come back after conventional treatment. Temozolomide (Temodar) is an anti-cancer drug that works by interfering with the growth of cells (including cancer cells) by stopping their division. Temozolomide was approved by the U.S. FDA for the treatment of newly diagnosed GBM in 2005. Avastin and temozolomide are currently being used together in several research studies involving people with newly diagnosed GBM. Limited information is available about either the safety or effectiveness of this drug combination.

Conditions

Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (2)

• Objective Response

  The best clinical response rates determined and 95% confidence intervals obtained using the exact binomial distribution.

  Up to 3 years

• Progression-free Survival (PFS)

  Up to 3 years

Secondary Outcomes (4)

• Safety of Avastin in Combination With Temozolomide in This Study Population

  Up to 3 years

• Duration of Response

  Up to 2 years

• Overall Survival

  Up to 3 years

• Changes in Relative Cerebral Blood Volume (rCBV) of Tumors After (2 Infusions) of Avastin

  Up to 3 years

Study Arms (1)

one

EXPERIMENTAL

This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).

Drug: Bevacizumab and Temozolomide

Interventions

Bevacizumab and Temozolomide DRUG

This is an open-label, single arm, multi-center, phase II study involving 48 subjects with newly diagnosed supra-tentorial GBM. Following surgery, subjects with radiographically evaluable disease will receive external beam radiotherapy (59.4 - 60 Gy in 30 - 33 fractions) with daily temozolomide (75 mg/m2). Two to three weeks later, subjects will begin treatment with temozolomide (150-200 mg/m2 daily for five of 28 consecutive days) in conjunction with Avastin (10 mg/kg, every 14 days).

Also known as: Avastin

one

Eligibility Criteria

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

You may qualify if:

• Disease-Specific Concerns Histologically confirmed GBM as determined by central pathology review Supratentorial location
• General Medical Concerns 18 years of age; Karnofsky performance status \> 60; Tumor-related contrast enhancement on initial and post-operative Gd-MRI; Recovery from effects of surgery and/or its complications prior to initiating radiotherapy; Radiotherapy must begin \< 5 weeks following surgery; Pre-and post-operative Gd-MRI prior to the initiation of radiotherapy; Adequate hematological, renal, and hepatic function:hemoglobin \> 10 grams hematocrit \> 30%, platelets \> 100,000 per mm3, BUN \< 25 mg/dl, Creatinine \< 1.5 mg/dl, Total bilirubin \< 1.5 mg/dl, SGOT or SGPT \< twice institutional normal range, Subjects must not be pregnant or nursing, Use of effective means of contraception (men and women) in subjects of child-bearing (women) and at all ages (men), Study-specific signed informed consent, Ability to comply with study follow-up procedures.

You may not qualify if:

• Subjects meeting any of the following criteria are ineligible for study entry:
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study; History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix);Pregnant or nursing females; Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmias requiring medication;
• Screening clinical laboratory values:
• Absolute neutrophil count \< 1500/ul, Platelet count \< 100,000/ul, Total bilirubin \> 1.6 mg.dl, AST/ALT \> 1.5 x the upper limit of normal ( ULN), Creatinine \> 1.2 x ULN, Urine protein/creatinine ratio \> 1.0, International normalized ration (INR) \> 1.5 and activated partial thromboplastin time (aPTT) \> 1.5 x ULN (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted.

Sponsors & Collaborators

• University of Chicago: lead
• Genentech, Inc.: collaborator

Study Sites (5)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

NorthShore University health system

Evanston, Illinois, 60201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48103, United States

Location

Medical college of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Waukesha health care

Waukesha, Wisconsin, 53188, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Bevacizumab; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Amanda Spratt
• Organization: University of Chicago

aspratt@bsd.uchicago.edu

773-834-4031

Study Officials

• Martin Kelly Nicholas, MD PhD

  University of Chicago

  PRINCIPAL INVESTIGATOR

• Martin Kelly Nicholas, MD, PhD

  University of Chicago

  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

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 11, 2008
• Study Start: February 1, 2007
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: March 30, 2021
• Results First Posted: March 1, 2021

Record last verified: 2021-03

Locations

US (5)