Tipifarnib, Temzolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma - Full Text View

Sponsors and Collaborators:	North American Brain Tumor Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049387

Purpose

RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining tipifarnib, temozolomide, and radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with temozolomide and radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: temozolomide Drug: tipifarnib Procedure: adjuvant therapy Procedure: radiation therapy	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Tipifarnib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I Trial Of R115777 With Radiation Therapy and Temzolomide In Patients With Newly Diagnosed Glioblastoma Multiforme

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

Study Start Date:

September 2002

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of tipifarnib when given in combination with temozolomide and radiotherapy followed by adjuvant tipifarnib and temzolomide in patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
Determine the safety of this regimen in these patients.
Determine any evidence of antitumor activity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes [closed to accrual as of 3/15/05] vs no).

Combination therapy: Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within 5-9 days after beginning tipifarnib, patients receive oral temozolomide once daily for 6 weeks and concurrently undergo partial brain radiotherapy daily 5 days a week for 6 weeks. After completion of radiotherapy, patients proceed to adjuvant therapy.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD.

Adjuvant therapy: Patients continue to receive tipifarnib as above. With the initiation of the next planned course of tipifarnib, patients receive oral temozolomide on days 1-5. Treatments repeats every 28 days for 12 courses OR 1 year (whichever is longer) in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients with progressive disease are followed at 10 weeks and then every 4 months. Patients who complete therapy are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter until disease progression.

PROJECTED ACCRUAL: Approximately 9-19 patients will be accrued for this study within 6 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed intracranial glioblastoma multiforme or gliosarcoma
- Established by biopsy or resection within the past 4 weeks
Planned external beam partial brain radiotherapy to begin within 5-9 days after beginning study drug and within 35 days of prior diagnostic biopsy or resection
- No concurrent stereotactic radiosurgery or brachytherapy
- Planned total dose to tumor of 60.0 Gy in daily fractions of 2.0 Gy

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 60-100%

Life expectancy

More than 8 weeks

Hematopoietic

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL (transfusions allowed)

Hepatic

Bilirubin less than 2 times upper limit of normal (ULN)
SGOT less than 2 times ULN

Renal

Creatinine less than 1.5 mg/dL

Other

No active infection
No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
No other significant uncontrolled medical illness that would preclude study participation
No disease that would obscure toxicity or dangerously alter drug metabolism
No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent immunotherapy
No concurrent sargramostim (GM-CSF)
No concurrent filgrastim (G-CSF) during first course of therapy

Chemotherapy

No prior polifeprosan 20 with carmustine implant
No concurrent chemotherapy

Endocrine therapy

Prior corticosteroids allowed
Concurrent corticosteroids allowed
No concurrent hormonal therapy

Radiotherapy

See Disease Characteristics
No prior radiotherapy to the brain

Surgery

See Disease Characteristics

Other

Prior enzyme-inducing antiepileptic drugs (EIAEDs), analgesics, or other drugs to treat symptoms or prevent complications are allowed
No prior cytotoxic, noncytotoxic, or experimental drug therapy for this disease
No other concurrent investigational drugs
No concurrent participation in another clinical study
No other concurrent drug therapy for this disease
No concurrent chronic warfarin except for deep venous thrombosis or pulmonary embolism
Concurrent EIAEDs, analgesics, or other drugs to treat symptoms or prevent complications are allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049387

Locations

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0316
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390-9154
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

North American Brain Tumor Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Timothy F. Cloughesy, MD

Jonsson Comprehensive Cancer Center

More Information

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

Web site for additional information This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000258059, NABTC-0202, NCI-03-C-0189
Study First Received:	November 12, 2002
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00049387
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Study placed in the following topic categories:

Glioblastoma
Astrocytoma
Central Nervous System Neoplasms
Temozolomide
Neuroectodermal Tumors
Glioblastoma multiforme
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Glioma
Gliosarcoma
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial
Tipifarnib

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Nervous System Diseases
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009