Clinical trial NCT00058097: Tipifarnib and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Official title: Phase II Study of R115777 for the Treatment of Adults With Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-04-09
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II trial to study the effectiveness of combining tipifarnib with radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining tipifarnib with radiation therapy may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

Detailed description: PRIMARY OBJECTIVES:

I. To estimate overall survival in newly diagnosed patients with glioblastoma multiforme treated with R115777 before (and possibly after) radiation therapy.

SECONDARY OBJECTIVES:

I. To estimate response rate in adult patients with newly diagnosed glioblastoma multiforme treated with R115777 prior to therapy with radiation.

II. To estimate progression free survival in newly diagnosed patients with glioblastoma multiforme treated with R115777 before (and possibly after) radiation therapy.

III. To describe the toxicity associated with this regimen in adult patients with newly diagnosed glioblastoma multiforme.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY: Patients receive oral tipifarnib twice daily for 3 weeks. Treatment repeats every 4 weeks for up to 3 courses.

RADIOTHERAPY: Within 14 days after the completion of induction therapy, patients undergo radiotherapy daily, 5 days a week, for 6 weeks.

MAINTENANCE THERAPY: Two weeks after the completion of radiotherapy, patients receive additional tipifarnib as in induction therapy.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A minimum of 54 patients will be accrued for this study within 11-14 months.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme)
* Patients must not have received prior radiation therapy, chemotherapy, hormonal therapy, immunotherapy or therapy with biologic agents (including immunotoxins immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy) or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed
* Patients must have measurable and contrast-enhancing tumor on the post operative, pretreatment MRI/CT scan (within two weeks of starting treatment)
* Patients must have recovered from the immediate post-operative period and be maintained on a stable corticosteroid regimen from the time of their baseline scan until the start of treatment
* Patients must have a Karnofsky performance status \>= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
* Absolute neutrophil count \>= 1500/mm\^3
* Platelets \>= 100,000/mm\^3
* Hemoglobin \>= 9 g/dl
* Creatinine =\< 1.5 mg/dl
* Total bilirubin =\< 2.0 mg/dl
* Transaminases =\< 4 times above the upper limits of the institutional norm
* Patients must be able to provide written informed consent and must be aware of the investigational nature of this study
* Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant; female patients of child-bearing potential must have a negative pregnancy test
* Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast; patients with prior malignancies must be disease-free for \>= five years
* Patients must have a mini-mental state exam score (MMSE) of \>= 15

Exclusion Criteria:

* Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the chemotherapy outlined in this protocol with reasonable safety
* Patients who are pregnant or breast-feeding
* Patients who have received prior radiation therapy, chemotherapy, hormonal therapy (except glucocorticoids), immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy) for their brain tumor
* Patients receiving concurrent investigational agents
* Patients who have received Gliadel wafer therapy may not participate in this study

Primary outcomes:
measure: Overall survival
timeFrame: Up to 5 years
Secondary outcomes:
measure: Response rate
timeFrame: Up to 5 years
measure: Progression free survival
timeFrame: Up to 5 years
measure: Toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v4.0
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: New Approaches to Brain Tumor Therapy Consortium
state: Maryland
Study officials:
affiliation: New Approaches to Brain Tumor Therapy Consortium
name: Robert Lustig
role: PRINCIPAL_INVESTIGATOR
References: