Erlotinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Condition: Adult Brain Tumors
MeSH terms: Glioblastoma; Brain Neoplasms; Gliosarcoma
Intervention: erlotinib hydrochloride
Intervention description: Tarceva will be self-administered in an open-label, unblinded manner to all patients enrolled in the study. 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.
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult glioblastoma; adult gliosarcoma; recurrent adult brain tumor

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.
    

Eligibility criteria:

        INclusion Criteria:

          -  Diagnosis of glioblastoma multiforme (GBM) or gliosarcoma (GS)

               -  In first, second, or third relapse

               -  History of low-grade glioma with transformation to GBM or GS allowed

                    -  Considered to be in first relapse at first documented diagnosis of GBM or GS

          -  Measurable or evaluable disease by contrast MRI

          -  Must have failed prior treatment that included external beam radiotherapy with or
             without chemotherapy

          -  Epidermal growth Factor Receptor-positive and PTEN wild-type by immunohistochemistry

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 60-100%

          -  WBC ≥ 3,000/mm³

          -  Absolute neutrophil count ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 10 g/dL (transfusion allowed)

          -  SGOT < 2 times upper limit of normal (ULN)

          -  Bilirubin < 2 times ULN

          -  Creatinine < 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective hormonal or barrier method contraception before,
             during, and for at least 12 weeks after completion of study treatment

          -  No other cancer within the past 3 years except nonmelanoma skin cancer or carcinoma in
             situ of the cervix

          -  No active infection

          -  No other disease that would obscure toxicity or dangerously alter study drug
             metabolism

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  More than 4 weeks since prior and no concurrent radiotherapy

          -  At least 4 weeks since prior and no concurrent cytotoxic chemotherapy agents (e.g.,
             temozolomide) (6 weeks for nitrosoureas)

          -  At least 2 weeks since prior and no concurrent noncytotoxic chemotherapy agents

          -  At least 4 weeks since prior investigational agents

          -  No other concurrent investigational agents

          -  No prior erlotinib hydrochloride or other epidermal growth factor receptor
             tyrosine-kinase inhibitors

          -  At least 2 weeks since prior enzyme-inducing antiepileptic drugs (EIAEDs), if not used
             concurrently with study treatment

               -  Concurrent continuous use of EIAEDs allowed provided the patient has received the
                  drug for ≥ 2 weeks prior to study treatment

          -  No concurrent immunotherapy or anticancer hormonal therapy

          -  No other concurrent antineoplastic or antitumor agents

        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.