Safety and Efficacy Study of Tarceva, Temodar, and Radiation Therapy in Patients With Newly Diagnosed Brain Tumors
Condition: Glioblastoma Multiforme; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Tarceva; Temodar; Radiation Therapy
Intervention description: 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; Temodar 200 mg/m^2/day x 5 days every 28 days; 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.
Intervention MeSH terms: Temozolomide; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 66.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma Multiforme; Gliosarcoma; GBM; GS; Tarceva; Temodar; Radiation; Newly Diagnosed

Summary:

      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.
    

Eligibility criteria:

        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.