Oral Tarceva Study for Recurrent/Residual Glioblastoma Multiforme and Anaplastic Astrocytoma
Oral Tarceva Study for Recurrent/Residual Glioblastoma Multiforme and Anaplastic Astrocytoma
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.
The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic
 astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of
 tumors also exhibits the most aggressive behavior, resulting in median overall survival
 durations of only 9-12 months for GBM, and 3-4 years for AA, from initial diagnosis, despite
 multimodal treatment approaches. Initial therapy consists of either surgical resection,
 external beam radiation or both. The role of adjuvant or concomitant chemotherapy in the
 initial therapy of GBM and AA has not, as yet, been clearly defined. Since most of these
 patients experience a recurrence after first-line therapy, improvements in both first-line
 and salvage therapy are critical to enhancing quality-of-life and prolonging survival. In
 August 2003, the U.S. Food and Drug Administration (FDA) granted orphan drug status for
 Erlotinib in patients with malignant glioma. Erlotinib (OSI-774) has been shown to be active
 in a range of tumors including GBM, AA and non small cell lung cancer. Because of the
 promising results in preliminary studies of Erlotinib and because of significant experience
 with the safety of the dosages proposed in this study, this study will offer a safe adjuvant
 treatment for patients with relapsing recurring glioblastoma or anaplastic astrocytoma.
 Therefore, this phase I/II clinical research trial will test the hypothesis that Erlotinib
 can be safely used up to a dose of 150 mg bid for 12 cycles to ultimately enhance survival of
 patients with relapsed/refractory GBM/AA with particular genetic alterations including
 EGFRvIII amplification and PTEN loss.
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.