Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma

NCT ID: NCT00525525

Last Updated: 2014-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2013-05-31

Brief Summary

This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately following a standard course of up-front radiotherapy and Temodar. All patients will receive Bevacizumab, Temodar and Tarceva. A total of 60 patients will be enrolled. Our hypothesis is that the combination of Bevacizumab plus Temodar and Tarceva will increase survival over that seen in historical controls who have newly diagnosed, non-progressive glioblastoma or gliosarcoma following radiotherapy plus Temodar and use Temodar alone.

Detailed Description

Patients with newly diagnosed glioblastoma or gliosarcoma are treated with standard of care radiation and temozolomide, plus the addition of Bevacizumab and Tarceva. The dose of temozolomide, Bevacizumab and radiation are the same for all patients. Tarceva dose is based upon the use of enzyme inducing anti-epileptic agents. Tarceva is given daily; Bevacizumab is given every 2 weeks; radiation is for 6 weeks, and temozolomide is given daily during radiotherapy and then in the adjuvant setting, is given on a 5-day schedule every 28 days. Patients are followed for progression and survival. The measure of response is MR scanning every 2 months. Dose adjustments are based upon the specific toxicity of the agent in question which differs for each agent (Bevacizumab, temozolomide, or Tarceva). Patients are not randomized, but assigned to an arm based on use of anti-epileptic agents.

Conditions

Glioblastoma; Gliosarcoma

Study Design

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

Study Groups

Efficacy Group

Patients treated with the combination of radiation plus temozolomide (75 mg/m2 daily during radiotherapy) plus bevacizumab (10 mg/kg IV every two weeks during radiotherapy) plus tarceva (dose based upon use of EIAED, either 200 mg daily or 500 mg daily; given daily); all treatment begins at the start of radiotherapy and continues until tumor progression, death or excessive toxicity

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Patients are given 10 mg/kg IV Q2 weeks.

Tarceva

Intervention Type: DRUG

Patients receive 150 mg PO daily. If patients are not experiencing intolerable toxicity, they may escalate their dose to 200 mg PO daily. If patients are experiencing intolerable toxicity, their dose will be held until the toxicity improves or resolves, then re-treated at a lower dose level, i.e. 100 mg PO daily.

Temozolomide

Intervention Type: DRUG

Patients receive 200 mg/m2 for Days 1-5 of every 28 day cycle. Although the calendar days may be slightly altered, the patient should always receive this dose for 5 days within a treatment cycle. If the patient experiences certain toxicities specified in the protocol, Temodar will be held then given at a reduced dose, i.e. 150 mg/m2 Days 1-5.

Safety Lead-in Group

Fractionated radiotherapy in daily doses of 1.8-2.0 Gy delivered 5 days per week over ~6 weeks, to a total dose of 59.4 to 60 Gy.

Adjuvant temozolomide 200 mg/m^2/d x 5 d per 28-d cycle; Erlotinib 150-200 mg/d (or 500-600 mg/d for patients on enzyme-inducing antiepileptic drugs) on a continuous basis 7 days per week; Bevacizumab 10 mg/kg every 2 weeks

Group Type: OTHER

Bevacizumab

Intervention Type: DRUG

Patients are given 10 mg/kg IV Q2 weeks.

Tarceva

Intervention Type: DRUG

Patients receive 150 mg PO daily. If patients are not experiencing intolerable toxicity, they may escalate their dose to 200 mg PO daily. If patients are experiencing intolerable toxicity, their dose will be held until the toxicity improves or resolves, then re-treated at a lower dose level, i.e. 100 mg PO daily.

Temozolomide

Intervention Type: DRUG

Patients receive 200 mg/m2 for Days 1-5 of every 28 day cycle. Although the calendar days may be slightly altered, the patient should always receive this dose for 5 days within a treatment cycle. If the patient experiences certain toxicities specified in the protocol, Temodar will be held then given at a reduced dose, i.e. 150 mg/m2 Days 1-5.

Interventions

Bevacizumab

Patients are given 10 mg/kg IV Q2 weeks.

Intervention Type: DRUG

Tarceva

Patients receive 150 mg PO daily. If patients are not experiencing intolerable toxicity, they may escalate their dose to 200 mg PO daily. If patients are experiencing intolerable toxicity, their dose will be held until the toxicity improves or resolves, then re-treated at a lower dose level, i.e. 100 mg PO daily.

Intervention Type: DRUG

Temozolomide

Patients receive 200 mg/m2 for Days 1-5 of every 28 day cycle. Although the calendar days may be slightly altered, the patient should always receive this dose for 5 days within a treatment cycle. If the patient experiences certain toxicities specified in the protocol, Temodar will be held then given at a reduced dose, i.e. 150 mg/m2 Days 1-5.

Intervention Type: DRUG

Other Intervention Names

Erlotonib

Eligibility Criteria

Inclusion Criteria

• Patients with histologically proven, non-progressive glioblastoma multiforme (GBM) or gliosarcoma (GS) with stable disease immediately following XRT + TMZ. All patients will receive Bevacizumab plus Tarceva and TMZ.
• Biopsy or resection must have been performed prior to RT + TMZ.
• No chemotherapy is allowed prior to starting RT + TMZ, including Gliadel Wafers.
• Patients will have started RT + TMZ prior to registration and study entry and are eligible as long as they do not have progressive disease and can start Bevacizumab + TMZ and Tarceva within 4 weeks after the completion of RT + TMZ. Patients MUST have been treated with at least 54 Gy radiotherapy (60 Gy recommended) and MUST have received Temodar concurrently with radiotherapy for eligibility for this study.
• Patients may or may not have measurable or evaluable disease on contrast MR imaging. A post-radiotherapy MRI scan must document stable disease.
• Patients must be > 18 years old and with a life expectancy > 12 weeks.
• Patients must have a Karnofsky performance status of ≥ 70.
• Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) before starting therapy. These tests must be performed within 14 days prior to initial treatment.

Exclusion Criteria

• Patients must not have evidence of recent hemorrhage on baseline MRI of the brain, with the following exceptions: presence of hemosiderin, resolving hemorrhage changes related to surgery, presence of punctuate hemorrhage in the tumor.
• Patients must not have any significant medical illnesses 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.
• Patients must not have proteinuria at screening as demonstrated by either

• Urine protein: creatinine (UPC) ratio ³ 1.0 at screening OR
• Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
• Patients must not have inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg) on antihypertensive medications.
• Patients must not have any prior history of hypertensive crisis or hypertensive encephalopathy.
• Patients must not have New York Heart Association Grade II or greater congestive heart failure (see Appendix E).
• Patients must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment.

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

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Michael Prados

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael D. Prados, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California San Francisco

San Francisco, California, United States

Countries

United States

References

Clarke JL, Molinaro AM, Phillips JJ, Butowski NA, Chang SM, Perry A, Costello JF, DeSilva AA, Rabbitt JE, Prados MD. A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro Oncol. 2014 Jul;16(7):984-90. doi: 10.1093/neuonc/nou029.

Reference Type: RESULT

PMID: 24637230 (View on PubMed)

Other Identifiers

07105

Identifier Type: -

Identifier Source: org_study_id

NCT00535249

Identifier Type: -

Identifier Source: nct_alias