Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

NCT ID: NCT00720356

Last Updated: 2018-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-07
• Study Completion Date: 2018-07-05

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works after radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

Detailed Description

OBJECTIVES:

Primary

• To determine the overall survival of patients with newly diagnosed glioblastoma multiforme (GBM) with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide.

Secondary

• To determine the 12- and 24-month progression-free survival (PFS) of patients with newly diagnosed GBM with unmethylated MGMT promoter treated with this regimen.
• To assess radiographic response rates.
• To perform correlative tissue assays.
• To collect safety data on the combination of bevacizumab and erlotinib hydrochloride in patients with newly diagnosed GBM with unmethylated MGMT promoter treated with bevacizumab and erlotinib hydrochloride after radiotherapy and temozolomide.

OUTLINE: This is a multicenter study.

Patients undergo radiotherapy (either intensity-modulated radiation therapy or 3-D conformal radiotherapy) once daily 5 days a week and receive oral temozolomide concurrently with radiotherapy once daily for 6 weeks (as planned). Patients whose tumor has a methylated MGMT promoter are removed from study.

Approximately 4 weeks after completion of radiotherapy and temozolomide, patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment with bevacizumab and erlotinib hydrochloride repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at approximately 30 days and then every 3 months thereafter.

Conditions

Brain and Central Nervous System Tumors

Study Design

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

Study Groups

Treatment

erlotinib and bevacizumab

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: DRUG

10mg/kg administered intravenously every 2 weeks

erlotinib hydrochloride

Intervention Type: DRUG

150 mg/daily orally

Interventions

bevacizumab

10mg/kg administered intravenously every 2 weeks

Intervention Type: DRUG

erlotinib hydrochloride

150 mg/daily orally

Intervention Type: DRUG

Other Intervention Names

Avastin; erlotinib; CP-358, 774; Tarceva

Eligibility Criteria

Inclusion Criteria

• Radiotherapy plans need to be verified to confirm the treatment plan meets the study requirement based on the PI assessment
• No progressive disease based on MRI or CT scan per the investigators assessment

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Life expectancy > 12 weeks
• WBC > 3,000/μL
• ANC > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 10 g/dL
• SGOT/SGPT < 3 times upper limit of normal (ULN)
• Bilirubin < 3 times ULN
• Creatinine < 1.5 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy, would compromise the patient's ability to tolerate this therapy, or any disease that will obscure toxicity or dangerously alter drug metabolism
• No proteinuria at screening, as demonstrated by either of the following:

• Urine protein:creatinine (UPC) ratio < 1.0
• Urine dipstick for proteinuria < 2+ OR ≤ 1g protein by 24-hour urine collection
• No inadequately controlled hypertension (defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg) on antihypertensive medications
• No history of hypertensive crisis or hypertensive encephalopathy
• No New York Heart Association class II-IV congestive heart failure
• No history of myocardial infarction or unstable angina within 6 months prior to study enrollment
• No history of stroke or transient ischemic attack within 6 months of study enrollment
• No symptomatic peripheral vascular disease
• No significant vascular disease (i.e., aortic aneurysm or aortic dissection)
• No evidence of bleeding diathesis or coagulopathy
• No significant traumatic injury within 28 days prior to study enrollment
• No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• No serious, nonhealing wound, ulcer, or bone fracture
• No known HIV positivity

• HIV testing is not required for study participation
• No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years

PRIOR CONCURRENT THERAPY:

• No chemotherapy is allowed prior to starting radiotherapy and temozolomide, including polifeprosan 20 with carmustine implant (Gliadel wafers)
• No major surgical procedure or open biopsy within 28 days prior to study enrollment or the anticipation of need for major surgical procedure during the course of the study
• No core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
• Concurrent nonenzyme-inducing anticonvulsants allowed

• More than 2 weeks (before starting erlotinib hydrochloride and bevacizumab) since prior and no concurrent enzyme-inducing anticonvulsant
• No other concurrent experimental agents
• Not concurrently participating in other clinical trials

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

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Raizer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey J. Raizer, MD

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, United States

Northwestern University, Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

Evanston Hospital

Evanston, Illinois, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Neuro-Oncology Associates at Baylor University Medical Center, Dallas

Dallas, Texas, United States

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

The Methodist Hospital Neurological Institute

Houston, Texas, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NU 07C3

Identifier Type: OTHER

Identifier Source: secondary_id

BTTC08-01

Identifier Type: OTHER

Identifier Source: secondary_id

STU00002792

Identifier Type: OTHER

Identifier Source: secondary_id

NU 07C3

Identifier Type: -

Identifier Source: org_study_id