Gefitinib and Radiation Therapy in Treating Patients With Glioblastoma Multiforme - Full Text View

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00052208

Purpose

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining gefitinib with radiation therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining gefitinib with radiation therapy in treating patients who have glioblastoma multiforme.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: gefitinib Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: ZD1839

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

June 2003

Detailed Description:

OBJECTIVES:

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

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.

PROJECTED ACCRUAL: 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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/mm^3
Platelet count at least 100,000/mm^3

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052208

Show 76 Study Locations

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Arnab Chakravarti, MD

Massachusetts General Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Study ID Numbers:	CDR0000069330, RTOG-0211, RTOG-BR-0211
Study First Received:	January 24, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00052208 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:

Glioblastoma
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Astrocytoma
Antineoplastic Agents
Nervous System Diseases
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Central Nervous System Neoplasms
Protein Kinase Inhibitors
Pharmacologic Actions

Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Glioma
Neoplasms, Neuroepithelial
Gefitinib
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 09, 2009