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

NCT00525525 | Completed Phase 2 Results DMC

• 1 other identifier: 07105
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Gliosarcoma

Keywords

Glioblastoma; Gliosarcoma; Bevacizumab; Avastin; Erlotinib; Tarceva; Temozolomide; Temodar

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  Overall survival was defined from the date of diagnosis to date of death from any cause

  Approximately 6-24 months

• Unexpected Toxicities During First 2 Cycles of Study Drug

  Unexpected severe study-related adverse events

  Within 8 weeks of initiating study therapy

Secondary Outcomes (1)

• Progression-free Survival

  Approximately 6 months to 1 year

Study Arms (2)

Efficacy Group

EXPERIMENTAL

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

Drug: Bevacizumab; Drug: Tarceva; Drug: Temozolomide

Safety Lead-in Group

OTHER

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

Drug: Bevacizumab; Drug: Tarceva; Drug: Temozolomide

Interventions

Bevacizumab DRUG

Patients are given 10 mg/kg IV Q2 weeks.

Efficacy Group; Safety Lead-in Group

Tarceva 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.

Also known as: Erlotonib

Efficacy Group; Safety Lead-in Group

Temozolomide 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.

Efficacy Group; Safety Lead-in Group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• 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.

  PMID: 24637230 RESULT

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Bevacizumab; Erlotinib Hydrochloride; 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; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Michael D. Prados, MD, FACP
• Organization: University of California San Francisco

pradosm@neurosurg.ucsf.edu

415-353-2383

Study Officials

• Michael D. Prados, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 4, 2007
• First Posted: September 5, 2007
• Study Start: September 1, 2007
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: November 14, 2014
• Results First Posted: November 14, 2014

Record last verified: 2014-11

Locations

US (1)