Safety and Efficacy Study of Tarceva, Temodar, and Radiation Therapy in Patients With Newly Diagnosed Brain Tumors

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00187486
First received: September 13, 2005
Last updated: September 26, 2012
Last verified: September 2012

September 13, 2005
September 26, 2012
August 2004
March 2011   (final data collection date for primary outcome measure)
Overall Survival [ Time Frame: assessment of survival was every 2 months, up to 181 weeks ] [ Designated as safety issue: No ]
Patients were monitored until death
Overall survival
Complete list of historical versions of study NCT00187486 on ClinicalTrials.gov Archive Site
Progression Free Survival [ Time Frame: every 2 months measure by MR imaging, up to 39 months ] [ Designated as safety issue: No ]
Progression based on MR imaging using the Modified McDonnald Criteria defined as 25% increase in sum of products of all measured lesions or any new lesion
  • 12-month survival rate and median time to tumor progression
  • Toxicity
  • Correlation of molecular phenotype of the tumor w/ survival
Not Provided
Not Provided
 
Safety and Efficacy Study of Tarceva, Temodar, and Radiation Therapy in Patients With Newly Diagnosed Brain Tumors
Phase II Study of Tarceva Plus Temodar During and Following Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme and Gliosarcoma

The patients eligible for this study are those diagnosed with glioblastoma or gliosarcoma who have recently undergone surgery and who have not been treated with radiation therapy or chemotherapy. This is called a phase II study. The purpose of the phase II study is to determine how effective Tarceva plus Temodar plus radiation is in controlling the growth of glioblastoma and gliosarcoma. All patients will receive radiation and Temodar plus Tarceva. There is no "placebo" drug.

This is a Phase II Study of Tarceva plus Temodar during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma. The efficacy and safety profile of Tarceva in combination with radiation therapy plus Temodar will be studied. In addition, correlations between response to treatment and epidermal growth factor receptor (EGFR) status as well as other molecular markers of tumor prior to treatment will be explored. Patients will be stratified according to enzyme inducing anti epileptic drug (EIAED) use. Group A (not on EIAEDs) will take 100 milligrams (mg) Tarceva/day during radiotherapy and start with a dose of 150 mg Tarceva/day two weeks after radiotherapy. Group B (on EIAEDs) will take 200mg Tarceva/day during radiotherapy and start with a dose of 300 mg Tarceva/day two weeks after radiotherapy. Both groups will take 75 mg/m^2 Temodar/day during radiotherapy and 200 mg/m^2 Temodar/day x 5 two weeks after radiotherapy. Intrapatient Tarceva dose escalation may occur every two weeks after radiotherapy until the appearance of a particular rash severity. The maximum dose allowed is 200 mg for group A and 500 mg for group B.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Glioblastoma Multiforme
  • Gliosarcoma
  • Drug: Tarceva
    Tarceva (erlotinib hydrochloride; previously referred to as OSI-774), a quinazoline, is an orally active, potent, selective inhibitor of EGFR tyrosine kinase. 100 - 300 milligrams (mg) every day (QD) orally (PO) every (q) 28 days depending on EIAED Status
    Other Name: erlotinib
  • Drug: Temodar
    Temodar 200 mg/m^2/day x 5 days every 28 days
    Other Name: temozolomide
  • Procedure: Radiation Therapy
    Radiotherapy will be administered in 180 centigray(cGy)/day - 200cGy/day fractions delivered 5 days per week to a total dose of 5940cGy - 6100cGy. A total of 4500cGy will be delivered to the clinical tumor volume consisting of T2-bright edema + a 2centimeter margin, or, if no edema, the contrast enhancing lesion +2.5 centimeter margin. An additional boost of 1440cGy will be delivered to the gross tumor volume consisting of the contrast enhancing lesion + a 1 centimeter margin.
    Other Name: radiation therapy
Experimental: Temodar plus Tarceva plus Radiotherapy
Single arm phase-2 experimental treatment of newly diagnosed patients with Glioblastoma with Temodar plus Tarceva plus Radiotherapy
Interventions:
  • Drug: Tarceva
  • Drug: Temodar
  • Procedure: Radiation Therapy
Prados MD, Chang SM, Butowski N, DeBoer R, Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler J, Rabbitt J, Page M, Fedoroff A, Sneed PK, Berger MS, McDermott MW, Parsa AT, Vandenberg S, James CD, Lamborn KR, Stokoe D, Haas-Kogan DA. Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol. 2009 Feb 1;27(4):579-84. Epub 2008 Dec 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
66
March 2011
March 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with histologically proven intracranial glioblastoma multiforme (GBM) and gliosarcoma (GS) will be eligible for this protocol.
  • Diagnosis will have been established by biopsy or resection no more than 5 weeks prior to treatment.
  • An magnetic resonance imaging (MRI) or computer tomography (CT) must be obtained within 14 days of treatment. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for assessment of tumor status.
  • Patients without measurable or assessable disease are eligible.
  • Patient must not have had prior cranial radiation therapy.
  • Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
  • Patients who received Gliadel wafers at the time of original resection will be excluded.
  • Patients must have a plan to begin partial brain radiotherapy the same day as Tarceva and temozolomide.
  • Radiotherapy must be a) at the Radiation Oncology Department of the University of California San Francisco or b) at an affiliated site such that a radiation oncologist at UCSF can provide assurance that radiation can be performed as specified.
  • Radiotherapy must be given by external beam to a partial brain field in daily fractions of 1.8 to 2.0 Gy, to a planned total dose to the tumor of 5940-6100 cGy.
  • Stereotactic radiosurgery and brachytherapy will not be allowed.
  • Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with Tarceva and temozolomide.
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
  • Patients must be registered in the UCSF Neuro-Oncology database prior to treatment with study drug.
  • Patients must sign an authorization for the release of their protected health information.
  • Patients must be 18 years or older, and with a life expectancy > 12 weeks.
  • Patients must have a Karnofsky performance status of > 60.
  • Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm^3, platelet count of > 100,000/mm^3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT, and bilirubin < 2 times ULN), and adequate renal function (creatinine < 1.5 mg/dL or calculated creatinine clearance > 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion.
  • Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
  • Patients with a history of any other cancer (except non-melanoma 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 are ineligible.
  • This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race.
  • Patients must not have active infection.
  • Patients must not be pregnant/breast feeding and must agree to practice adequate contraception.
  • Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration.
  • Patients must not be pregnant because of the uncertainty that study drug may be potentially embryotoxic. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study participation, and continue approximately 12 weeks after the study is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
  • Patients must not have serious inter-current medical illness.
  • Patient with recent thromboembolic disease (deep vein thrombosis and pulmonary embolism) are eligible if they are clinically stable and the thromboembolic event occurred more than 3 weeks prior to enrollment into this protocol.

Exclusion Criteria:

  • Patients who do not meet one or more of the inclusion criteria above.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00187486
CC 04101, OSI 2725s
Yes
University of California, San Francisco
University of California, San Francisco
Genentech
Principal Investigator: Michael Prados, MD UCSF Department of Neurological Surgery
University of California, San Francisco
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP