Erlotinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

Phase 2

Terminated

Brief Summary: RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with recurrent glioblastoma multiforme or gliosarcoma.

Detailed Description: OBJECTIVES:

Primary

* Determine the objective response rate in patients with recurrent epidermal growth factor receptor (EGFR)-positive and PTEN wild-type glioblastoma multiforme or gliosarcoma treated with erlotinib hydrochloride.

Secondary

* Assess the response rate in patients who also EGFRVIII mutant and PTEN wild type glioblastoma multiforme or gliosarcoma.

* Determine the progression-free survival of patients treated with this drug.

OUTLINE: This is an open-label study. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no).

Patients receive oral erlotinib hydrochloride once daily on days 1-28. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Some patients may receive additional erlotinib hydrochloride after 1 year at their physician's discretion.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Patients meeting any of the following criteria are ineligible for study entry:

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.
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 14 days prior to treatment. 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. If condoms are used as a barrier contraceptive, a spermicidal agent should be added to ensure that pregnancy does not occur. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Prior treatment with Tarceva, or other EGFR tyrosine-kinase inhibitors will not be allowed.
Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.

Arm && Interventions

Group	Intervention	Description
erlotinib hydrochloride (Tarceva)	erlotinib hydrochloride	During the treatment period, patients who are not receiving EIAED (Group A) will receive single-agent Tarceva, 150 mg/day. Patients on EIAED (Group B) will receive single-agent Tarceva, 600 mg/day. Tablets should be taken at the same time each day with 200 mL of water at least 1 hour before or 2 hours after a meal. Patients who are unable to swallow tablets may dissolve the tablets in distilled water for administration. The dose of Tarceva will be escalated after 14 days to 200 mg/day (Group A) or 650 mg/day (Group B) assuming no intolerable grade 2 rash, any grade 3 rash, or grade 2 diarrhea despite loperamide.

Primary Outcome Measures

Name	Time	Method
Disease Response Measured Objectively by MRI of Brain	Every 8 weeks or as indicated	Lack of disease progression indicates response to treatment

Secondary Outcome Measures

Name	Time	Method
Duration of Progress-free Survival (PFS)	Until first observation of progressive disease, non-reversible neurologic progression or permanently increased steroid requirement (stable disease only), death due to any cause (up to 16 weeks)	Patients with stable or responding disease will continue treatment until tumor progression is determined