Gefitinib in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase II Study Of ZD1839 (NSC 715055) In Newly Diagnosed Patients With Glioblastoma (Grade 4 Astrocytoma)

Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of glioblastoma multiforme. Phase II trial to study the effectiveness of gefitinib in treating patients who have newly diagnosed glioblastoma multiforme.

Study Overview

• Status: Completed
• Conditions: Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: gefitinib; Other: questionnaire administration; Procedure: quality-of-life assessment; Other: pharmacological study

Detailed Description

OBJECTIVES:

I. Determine treatment effectiveness of gefitinib, in terms of response rate, time to progression, survival at 52 weeks, progression-free survival at 6 months, and overall survival, in patients with newly diagnosed glioblastoma multiforme.

II. Determine the toxic effects of this drug in these patients. III. Assess fatigue, depression, excessive daytime somnolence, and quality of life in patients treated with this drug.

IV. Assess individual variation in responses, pharmacokinetic parameters, and/or biological correlates due to genetic differences in enzymes involved in transport, metabolism, and/or mechanism of action of this drug in these patients.

V. Determine if the type of epidermal growth factor receptor affects tumor response and outcome in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral gefitinib daily. Courses repeat every 8 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each treatment course, every 4 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Patients are followed every 8 weeks until tumor progression and then every 3 months for 5 years and annually for up to 10 years. Patients removed from study treatment for reasons other than disease progression are followed every 4 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study within 14 months.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed newly diagnosed WHO grade IV astrocytoma (glioblastoma multiforme) or gliosarcoma

  • No WHO grade III anaplastic astrocytoma, oligodendroglioma, or mixed oligoastrocytoma

• Completed standard external beam radiotherapy within the past 2-5 weeks

  • No evidence of tumor progression during radiotherapy
• Performance status - ECOG 0-2
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN
• Creatinine no greater than 1.5 times ULN
• No other active malignancy
• No uncontrolled infection
• No other severe concurrent disease that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior chemotherapy (including polifeprosan 20 with carmustine implant) for this tumor
• See Disease Characteristics
• No prior stereotactic radiosurgery or interstitial brachytherapy
• No more than 15 weeks since prior surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (gefitinib); Patients receive oral gefitinib daily. Courses repeat every 8 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: gefitinib; Given orally; Other Names: Iressa; ZD 1839; Other: questionnaire administration; Ancillary studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	The proportion of 'successes' will be estimated using the binomial point estimator (number of 'successes' divided by the total number of evaluable patients) and standard binomial 90% confidence interval estimates. In the unlikely event that accrual has not been completed before the interim analyses are performed, the Duffy-Santner lgorithm will be used to calculate 90% confidence intervals.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-RT progression-time	Kaplan-Meier survival curves and logrank tests will be used.	From start of study therapy to date of disease progression or last follow-up, assessed up to 10 years
Toxicity patterns assessed using NCI CTC version 2.0	Will be analyzed descriptively. Toxicity score calculated as the sum of the maximum toxicity grades recorded for each of the types of adverse reactions observed during the trial.	Up to 10 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Joon Uhm, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): July 1, 2003

Study Registration Dates

• First Submitted: April 10, 2001
• First Submitted That Met QC Criteria: June 9, 2003
• First Posted (Estimate): June 10, 2003

Study Record Updates

• Last Update Posted (Estimate): July 16, 2013
• Last Update Submitted That Met QC Criteria: July 15, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Gliosarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: NCI-2012-01855; U10CA025224 (U.S. NIH Grant/Contract); N0074; CDR0000068511; NCCTG-N0074