Tipifarnib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT02227901 | Completed Phase 1

• 6 other identifiers: NCI-2014-01809NCI-03-C-0189NABTC-0202NABTC02-02NABTC-02-02U01CA062399
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of tipifarnib when given together with radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme. Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tipifarnib together with radiation therapy and temozolomide may be a better way to treat glioblastoma multiforme.

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) of tipifarnib, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0

  Safety variables will be summarized by descriptive statistics.

  At week 10

• MTD of tipifarnib, defined as the dose level at which 0 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT, graded according to the NCI CTCAE v4.0

  Safety variables will be summarized by descriptive statistics.

  Up to week 10

Secondary Outcomes (2)

• Incidence of adverse events of tipifarnib in combination with EBRT and temozolomide, graded according to the NCI CTCAE v4.0

  Up to 5 years

• Anti-tumor activity of tipifarnib

  Up to 5 years

Study Arms (1)

Treatment (tipifarnib, EBRT, temozolomide)

EXPERIMENTAL

TIPIFARNIB: Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. CONCURRENT CHEMOTHERAPY DURING RADIATION THERAPY: Within 5-9 days after starting tipifarnib, patients undergo EBRT daily and receive temozolomide PO daily for 6 weeks. POST-RADIATION CHEMOTHERAPY: Beginning at week 10 post-radiation therapy, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for 1 year or 12 complete courses in the absence of disease progression or unacceptable toxicity.

Drug: Tipifarnib; Radiation: External Beam Radiation Therapy; Drug: Temozolomide; Other: Laboratory Biomarker Analysis

Interventions

Tipifarnib DRUG

Given PO

Also known as: R115777, Zarnestra

Treatment (tipifarnib, EBRT, temozolomide)

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam RT

Treatment (tipifarnib, EBRT, temozolomide)

Temozolomide DRUG

Given PO

Also known as: TMZ

Treatment (tipifarnib, EBRT, temozolomide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tipifarnib, EBRT, temozolomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 magnetic resonance imaging (MRI) or contrast computed tomography (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 Adult Brain Tumor Consortium (ABTC) institution; radiotherapy must be given by external beam to a partial brain field in daily fractions of 2.0 Gray (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
• A life expectancy \> 8 weeks
• Patients must have a Karnofsky performance status of \>= 60
• White blood cells (WBC) \>= 3,000/ul
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3
• Platelet count of \>= 100,000/mm\^3
• Hemoglobin \>= 10 gm/dl
• Bone marrow function tests must be performed within 14 days prior to registration

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

tipifarnib; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Timothy Cloughesy

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 28, 2014
• Study Start: September 1, 2002
• Primary Completion: June 1, 2007
• Study Completion: April 1, 2014
• Last Updated: December 23, 2014

Record last verified: 2014-09

Locations

US (1)