Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma - Full Text View

Sponsor:	University of California, San Francisco
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00525525

Purpose

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.

Condition	Intervention	Phase
Glioblastoma Gliosarcoma	Drug: Avastin Drug: Tarceva Drug: Temodar	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment
Official Title:	A Phase II Study of Bevacizumab Plus Temodar and Tarceva After Radiation Therapy and Temodar in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma Who Are Stable Following Radiation

Resource links provided by NLM:

Drug Information available for: Temozolomide Erlotinib hydrochloride Erlotinib Bevacizumab

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

To determine the overall and progression-free survival for non-progressive patients with newly diagnosed glioblastoma or gliosarcoma treated with Bevacizumab plus Temodar and Tarceva following radiation therapy and Temodar. [ Time Frame: Approximately 6 months to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To collect safety data on the combination of Bevacizumab plus Temodar and Tarceva for patients with non-progressive newly diagnosed glioblastoma or gliosarcoma treated with Bevacizumab and Tarceva after radiation therapy and Temodar. [ Time Frame: Approximately 6 months to 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	September 2007
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Patients are given 10 mg/kg IV Q2 weeks.

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00525525

Contacts

Contact: Valerie Kivett, BS

415-353-2076

kivettv@neurosurg.ucsf.edu

Locations

United States, California
University of California San Francisco	Recruiting
San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:

Michael D. Prados, MD

University of California, San Francisco

More Information

No publications provided

Responsible Party:	UCSF ( Michael Prados, MD )
Study ID Numbers:	07105, unknown
Study First Received:	September 4, 2007
Last Updated:	August 18, 2009
ClinicalTrials.gov Identifier:	NCT00525525 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:

Glioblastoma
Gliosarcoma
Bevacizumab
Avastin

Erlotinib
Tarceva
Temozolomide
Temodar

Additional relevant MeSH terms:

Glioblastoma
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Bevacizumab
Protein Kinase Inhibitors
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Glioma
Angiogenesis Modulating Agents
Growth Inhibitors
Alkylating Agents
Erlotinib

Neoplasms by Histologic Type
Astrocytoma
Growth Substances
Enzyme Inhibitors
Temozolomide
Angiogenesis Inhibitors
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Gliosarcoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 20, 2009