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

Northwestern University

Status and phase

Completed

Phase 2

Conditions

Brain and Central Nervous System Tumors

Treatments

Drug: erlotinib hydrochloride

Drug: bevacizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT00720356

NU 07C3 (Other Identifier)

BTTC08-01 (Other Identifier)

STU00002792 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

115 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed newly diagnosed glioblastoma multiforme (GBM) or gliosarcoma
Undergoing or plan to undergo treatment with radiotherapy and concurrent temozolomide for 6 weeks
Unmethylated MGMT promoter status must be determined before completing radiotherapy
- Tumor must be MGMT negative to receive bevacizumab and erlotinib hydrochloride
Patients who are post biopsy or tumor resection allowed provided a post-operative MRI is done no more than 96 hours after surgery (in order for an accurate assessment to be done post radiotherapy):
- Evaluable or measurable disease after resection of recurrent tumor is not mandated for eligibility
Patients who started radiotherapy and temozolomide prior to study entry are eligible as long as the gene methylation status is determined before starting bevacizumab and erlotinib hydrochloride
- 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