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Erlotinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma

This study has been terminated.
(Insufficient accrual of population likely to benefit; progression in 6 patients)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00387894
First Posted: October 13, 2006
Last Update Posted: June 4, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
Genentech, Inc.
Information provided by (Responsible Party):
Michael Prados, University of California, San Francisco
  Purpose

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.


Condition Intervention Phase
Adult Brain Tumors Drug: erlotinib hydrochloride Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Michael Prados, University of California, San Francisco:

Primary Outcome Measures:
  • Disease Response Measured Objectively by MRI of Brain [ Time Frame: Every 8 weeks or as indicated ]
    Lack of disease progression indicates response to treatment


Secondary Outcome Measures:
  • Duration of Progress-free Survival (PFS) [ Time Frame: 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


Enrollment: 6
Study Start Date: January 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: erlotinib hydrochloride (Tarceva)
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.
Drug: erlotinib hydrochloride
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.
Other Name: Tarceva

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00387894


Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94143
Sponsors and Collaborators
Michael Prados
National Cancer Institute (NCI)
Genentech, Inc.
Investigators
Principal Investigator: Michael D. Prados, MD University of California, San Francisco
  More Information

Responsible Party: Michael Prados, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00387894     History of Changes
Other Study ID Numbers: CDR0000492762
UCSF-06102 ( Other Identifier: OnCore )
UCSF-H5941-28905-01 ( Other Identifier: IRB Approval # )
GENENTECH-OSI3765s ( Other Identifier: Sponsor protocol ID )
First Submitted: October 12, 2006
First Posted: October 13, 2006
Results First Submitted: April 12, 2013
Results First Posted: May 17, 2013
Last Update Posted: June 4, 2013
Last Verified: April 2013

Keywords provided by Michael Prados, University of California, San Francisco:
adult glioblastoma
adult gliosarcoma
recurrent adult brain tumor

Additional relevant MeSH terms:
Glioblastoma
Brain Neoplasms
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action