Clinical trial NCT00387894: Erlotinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma
Official title: Phase-2 Study of Tarceva in Patients With Recurrent EGFR Positive and Phosphatase and Tensin Homolog (PTEN) Wild Type Glioblastoma Multiforme and Gliosarcoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adult Brain Tumors
Keywords: adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Genentech, Inc.
First posted: 2006-10-13
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Disease Response Measured Objectively by MRI of Brain
timeFrame: Every 8 weeks or as indicated
Secondary outcomes:
measure: Duration of Progress-free Survival (PFS)
timeFrame: 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)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Michael D. Prados, MD
role: PRINCIPAL_INVESTIGATOR
References: