Oral Tarceva Study for Recurrent/Residual Glioblastoma Multiforme and Anaplastic Astrocytoma

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will offer a safe treatment for patients with relapsing recurring glioblastoma (GBM) or anaplastic astrocytoma (AA). The trial will test the hypothesis that Erlotinib (Tarceva, OSI-774) can be safely used up to a dose of 150 mg two times a day for 12 months to ultimately enhance survival of patients with relapsed/refractory GBM/AA. Correlation of response to Tarceva with particular genetic alterations including epidermal growth factor receptor variant type III (EGFRvIII) amplification and phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) loss will be studied.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Northwell Health
• Collaborator: Genentech, Inc.
• Treatments: Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

• Male or female patients of ≥ 18 years of age.

• Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA). All patients will have samples of their tissue evaluated for EGFRvIII overexpression and PTEN loss.

• Patients with a histologically confirmed low grade brain tumor who relapse with an enhancing tumor on magnetic resonance imaging (MRI) can be evaluated for toxicity only.

• Patients must have at least one confirmed and evaluable tumor site.*

*A confirmed tumor site is one which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or computed tomography [CT] scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.

• Patients must have a Karnofsky performance status ≥ 60% (or the equivalent Eastern Cooperative Oncology Group [ECOG] level of 0-2) and an expected survival of ≥ three months.

• No chemotherapy for six weeks prior to treatment under this research protocol and no external beam radiation for eight weeks prior to treatment under this research protocol.

• Patients must have adequate hematologic reserve with WBC ≥ 3000/mm3, absolute neutrophils ≥ 1500/mm3 and platelets ≥ 100,000/mm3. Patients who are on Coumadin must have a platelet count of ≥ 150,000/mm3

• Pre-enrollment chemistry parameters must show: bilirubin < 1.5X the institutional upper limit of normal (IUNL); AST or ALT < 2.5X IUNL and creatinine < 1.5X IUNL.

• Pre-enrollment coagulation parameters (PT and PTT) must be ≤ 1.5X the IUNL.

• Concomitant Medications:

• Growth factor(s): Must not have received within 1 week of entry onto this study.

• Steroids: Systemic corticosteroid therapy is permissible in patients with centrail nervous system (CNS) tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.

• Study Specific: Patients on enzyme-inducing anticonvulsants will be changed to non-enzyme inducing anticonvulsants or will not be allowed on this study. Patients receiving proton pump inhibitor or H2 blockers will not be allowed on study. Patients taking antacids will be allowed on study although they should not take the antacid for two hours before or two hours after taking erlotinib.

• Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.

• Patients should not have received a CYP3A4 inhibitor within 1 week of study entry and should not have received a CYP3A4 inducer within 4 weeks of study entry.

• Patients should not have received proton-pump inhibitors within 5 days of study entry or H2 blockers within 2 days of study entry.

• Patients on steroids must receive prophylaxis for Pneumocystis carinii pneumonia (PCP) with Bactrim, unless they have a history of allergy to sulfa drugs.

• Patients must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening.

Exclusion Criteria:

• Previous treatment with Tarceva®.

• Women who are pregnant or lactating.

• Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.

• Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.