Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Gefitinib and Radiation Therapy in Treating Patients With Glioblastoma Multiforme

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	Adult	NCI	RTOG-0211 RTOG-BR-0211, NCT00052208

Objectives

1. Determine the maximum tolerated dose of gefitinib when given concurrently with cranial radiotherapy in patients with glioblastoma multiforme.
2. Determine the overall survival and progression-free survival of patients treated with this regimen.
3. Determine the feasibility and toxicity of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed glioblastoma multiforme with areas of necrosis
  • Tumor must be supratentorial
• Diagnosis made by surgical biopsy or excision
• No recurrent or multifocal disease
• No metastases detected below the tentorium or beyond the cranial vault
• Tumor tissue and serum samples required

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy or radiosensitizers for cancers of the head and neck

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the head and neck except for T1 glottic tumors

Surgery:

• See Disease Characteristics
• No more than 5 weeks since prior surgery and recovered
• No concurrent ophthalmic surgery

Other:

• At least 30 days since prior participation in another clinical study
• No concurrent participation in another clinical study
• No concurrent systemic retinoids or herbal medicines
• No concurrent drugs that induce CytP4503A4 except enzyme-inducing anticonvulsant drugs

Patient Characteristics:

Age:

• Adult

Performance status:

• Zubrod 0-1

Life expectancy:

• At least 8 weeks

Hematopoietic:

• Hemoglobin at least 10 g/dL (transfusions allowed)
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGPT or SGOT no greater than 2 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL
• BUN no greater than 25 mg/dL

Other:

• No known AIDS
• No other major medical illness or psychiatric impairment that would preclude study participation
• No active connective tissue disorders, including lupus and scleroderma
• No known multiple sclerosis
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 30 patients (18 enzyme-inducing anticonvulsant drug [EIACD] patients and 12 non-EIACD patients) will be accrued for phase I of this study within 2 months. A maximum of 140 patients will be accrued for phase II of this study within 10 months.

Outline

This is a multicenter, dose-escalation study of gefitinib. Patients are stratified according to whether they are concurrently receiving enzyme-inducing anticonvulsant drugs (EIACD) (yes vs no).

• Phase I:Patients receive oral gefitinib once daily for 7 weeks. Beginning 1 week after initiation of gefitinib, patients undergo cranial radiotherapy once daily 5 days a week for 6 weeks. After the completion of radiotherapy, patients continue to receive oral gefitinib once daily for 18 months in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II:Patient receive oral gefitinib at the MTD as in phase I. Patients undergo cranial radiotherapy as in phase I.

Patients in both phases are followed every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Chakravarti A, Berkey B, Robins HI, et al.: An update of phase II results from RTOG 0211: a phase I/II study of gefitinib with radiotherapy in newly-diagnosed glioblastoma multiforme. [Abstract] American Association for Cancer Research: 97th Annual Meeting, April 1-5, 2006, Washington, DC. 2006.

Chakravarti A, Seiferheld W, Robins HI, et al.: An update of phase I data from RTOG 0211: a phase I/II clinical study of gefitinib + radiation for newly-diagnosed glioblastoma (GBM) patients. [Abstract] J Clin Oncol 22 (Suppl 14): A-1571, 124s, 2004.

Chakravarti A, Seiferheld W, Robbins I, et al.: Phase I results from RTOG BR-0211, a phase I/II study of an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), ZD 1839 (Iressa), with radiation therapy in glioblastoma multiforme (GBM). [Abstract] Int J Radiat Oncol Biol Phys 57 (2 Suppl): S329, 2003.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Arnab Chakravarti, MD, Protocol chair(Contact information may not be current)		Ph: 617-726-2000; 877-726-5130

Registry Information
Official Title		A Phase I/II Study Of An Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), ZD 1839 (IRESSA) [NSC# 715055] With Radiation Therapy In Glioblastoma Multiforme
Trial Start Date		2003-06-08
Registered in ClinicalTrials.gov		NCT00052208
Date Submitted to PDQ		2002-03-08
Information Last Verified		2003-09-30
NCI Grant/Contract Number		CA21661

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