Overview

This trial is active, not recruiting.

Condition brain and central nervous system tumors
Treatments bevacizumab, erlotinib hydrochloride
Phase phase 2
Targets EGFR, VEGF
Sponsor Northwestern University
Collaborator M.D. Anderson Cancer Center
Start date March 2009
End date March 2018
Trial size 50 participants
Trial identifier NCT00720356, BTTC08-01, NU 07C3, STU00002792

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
erlotinib and bevacizumab
bevacizumab Avastin
10mg/kg administered intravenously every 2 weeks
erlotinib hydrochloride erlotinib
150 mg/daily orally

Primary Outcomes

Measure
Overall survival
time frame: Every 3 months following the end of treatment due to disease progression

Secondary Outcomes

Measure
Progression-free survival at 12 and 18 months
time frame: At 12 and 18 months after ending study treatment due to disease progression
Radiographic response rates
time frame: Every 8 weeks during treatment
Safety of the combination of erlotinib and bevacizumab in this patient population
time frame: Every 4 weeks during treatment and every 3 months during survival follow up

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title A Phase II Study of Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Without MGMT Promoter Methylation
Principal investigator Jeffrey J. Raizer, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Northwestern University.