Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
Overview
- Phase
- Phase 1
- Intervention
- tipifarnib
- Conditions
- Adult Giant Cell Glioblastoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Antitumor activity
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
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. 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.
Detailed Description
PRIMARY OBJECTIVES: I. Establish MTD for R115777 in combination with Temozolomide with radiation in patients not on EIAEDs. II. To define the safety of R115777 in combination with Temozolomide with radiation in this patient population. III. To assess for evidence of antitumor activity in this patient population. 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. Treatment 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS)
- •Diagnosis will have been established by biopsy or resection within 4 weeks prior to registration
- •Patients must not have received previous radiotherapy to the brain
- •Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent complications
- •Cranial MRI or contrast CT must have been performed within 21days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed with 96 hours of resection is preferred but not required; patients without measurable or assessable disease are eligible
- •Patients must have a plan to begin partial brain radiotherapy within 5-9 days after beginning R115777, and within 35 days (5 weeks) of the surgical procedure that established the diagnosis; radiotherapy must be given at the Radiation Oncology Department of the registering ABTC institution; radiotherapy must be given by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will not be allowed
- •Patients must be willing to forego other drug therapy against the tumor while being treated with R115777 and temozolomide
- •All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information; patients must be registered with the Adult Brain Tumor Consortium Central Office (ABTC CO) prior to treatment with study drug
- •Life expectancy \> 8 weeks
- •Patients must have a Karnofsky performance status of \>= 60
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (tipifarnib, temozolomide, radiation therapy)
See Detailed Description
Intervention: tipifarnib
Treatment (tipifarnib, temozolomide, radiation therapy)
See Detailed Description
Intervention: temozolomide
Treatment (tipifarnib, temozolomide, radiation therapy)
See Detailed Description
Intervention: radiation therapy
Outcomes
Primary Outcomes
Antitumor activity
Time Frame: Up to 5 years
MTD of tipifarnib
Time Frame: Week 10
Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.
Incidence of adverse events
Time Frame: Up to 5 years
Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.