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Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tipifarnib
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent adult brain tumor, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed intracranial primary malignant glioma Glioblastoma multiforme Anaplastic astrocytoma* Anaplastic oligodendroglioma* Anaplastic mixed oligodendroglioma* Malignant astrocytoma (not otherwise specified)* NOTE: *Closed to accrual effective 5/28/2002 Progressive or recurrent disease confirmed by MRI or CT scan within the past 14 days Stable steroid dose for at least 5-7 days Confirmation of true progressive disease by PET scan, thallium scan, MR spectroscopy, or surgery if prior therapy included interstitial brachytherapy or stereotactic radiosurgery Failed prior radiotherapy Phase I (phase I completed effective 10/2/2001): No more than 2 prior chemotherapy or cytotoxic regimens, including 1 prior adjuvant therapy and 1 prior regimen for progressive or recurrent disease, or 2 prior regimens for progressive disease Phase II (phase II open only to patients requiring resection and who provide surgical tissue samples [effective 3/13/2003]): No more than 2 prior chemotherapy or cytotoxic regimens for relapsed disease following initial therapy (radiotherapy with or without chemotherapy) Prior surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks followed by another surgical resection is considered 1 relapse Patients who received prior therapy for a low-grade glioma with a surgical diagnosis of a high-grade glioma are considered to be in first relapse 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 2,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL (transfusion allowed) Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN Renal: Creatinine less than 1.5 mg/dL Cardiovascular: No uncontrolled high blood pressure No unstable angina No symptomatic congestive heart failure No myocardial infarction within the past 6 months No serious uncontrolled cardiac arrhythmia Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No severe nonmalignant systemic diseases or active infections No other severe concurrent disease that would preclude study therapy No allergy to azoles (e.g., ketoconazole, itraconazole, or voriconazole) HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior interferon No concurrent anticancer immunotherapy No concurrent routine prophylactic filgrastim (G-CSF) during first course of study No concurrent sargramostim (GM-CSF) Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, suramin, or mitomycin) At least 3 weeks since prior procarbazine At least 2 weeks since prior vincristine No other concurrent anticancer chemotherapy Endocrine therapy: See Disease Characteristics At least 1 week since prior tamoxifen Concurrent corticosteroids allowed No concurrent anticancer hormonal therapy Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered No concurrent anticancer radiotherapy Surgery: See Disease Characteristics At least 3 weeks since prior resection and recovered Prior recent resection of recurrent or progressive tumor allowed Other: Recovered from all prior therapy (excluding neurotoxicity or alopecia) Prior radiosensitizers allowed Concurrent H2 blockers and antacids allowed provided taken at least 2 hours before and after tipifarnib No concurrent proton pump inhibitors (e.g., omeprazole or lansoprazole) No other concurrent medication that would preclude study therapy (e.g., immunosuppressive agents) No other concurrent anticancer therapy No other concurrent investigational drugs No concurrent participation in any other clinical study No other concurrent medications except analgesics, chronic treatments for concurrent medical conditions, or agents for life-threatening medical problems

Sites / Locations

  • Jonsson Comprehensive Cancer Center, UCLA
  • UCSF Comprehensive Cancer Center
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Memorial Sloan-Kettering Cancer Center
  • Hillman Cancer Center at University of Pittsburgh Cancer Institute
  • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
  • University of Texas - MD Anderson Cancer Center
  • University of Texas Health Science Center at San Antonio
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
June 2, 2000
Last Updated
June 22, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005859
Brief Title
Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma
Official Title
Phase I/II Trial of R115777 in Patients With Recurrent Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
May 16, 2000 (Actual)
Primary Completion Date
July 1, 2005 (Actual)
Study Completion Date
August 1, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating patients who have recurrent or progressive malignant glioma.
Detailed Description
OBJECTIVES: Determine the maximum tolerated dose of tipifarnib in patients with recurrent or progressive malignant glioma receiving enzyme-inducing antiepileptic drugs. (Stratum II in the phase I portion of this study closed to accrual effective 07/16/2001.) (Phase I completed effective 10/2/2001.) (Phase II open only to patients requiring resection and who provide surgical tissue samples [effective 3/13/2003].) Define the safety and pharmacokinetic profile of this drug in this patient population. Assess for evidence of antitumor activity of this drug in these patients. Assess for evidence of inhibition of farnesyl protein transferase (FTase) on peripheral blood monocytes as a surrogate endpoint of effective biologic activity of this drug in these patients. Determine the efficacy of this drug as measured by 6-month progression-free survival and objective tumor response in these patients. Evaluate further the safety profile of this drug in these patients. Correlate treatment response with inhibition of FTase in peripheral blood monocytes in patients treated with this drug. OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to their pretreatment medications (not receiving enzyme-inducing antiepileptic drugs [EIAEDs] vs receiving EIAEDs with or without steroids). Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 4 weeks in the absence of unacceptable toxicity or disease progression. Phase I (completed 10/2/2001): Cohorts of 3-6 patients from stratum II receive escalating doses of tipifarnib 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. (Stratum II in the phase I portion of this study closed to accrual effective 07/16/2001.) Phase II (open only to patients requiring resection and who provide surgical tissue samples [effective 3/13/2003]): Once the MTD is determined, additional patients with glioblastoma multiforme from stratum II are accrued to receive treatment with tipifarnib at the recommended phase II dose. Patients 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 until progression. Patients are then followed every 4 months thereafter. PROJECTED ACCRUAL: Approximately 30 patients (15 per stratum) will be accrued for the phase I portion of this study within 10 months. (Stratum II in the phase I portion of this study closed to accrual effective 07/16/2001.) (Phase I completed effective 10/2/2001.) A total of 24 patients with glioblastoma multiforme from stratum II will be accrued for the phase II portion of this study. (Phase II open only to patients requiring resection and who provide surgical tissue samples [effective 3/13/2003].)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
recurrent adult brain tumor, adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
136 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
tipifarnib

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed intracranial primary malignant glioma Glioblastoma multiforme Anaplastic astrocytoma* Anaplastic oligodendroglioma* Anaplastic mixed oligodendroglioma* Malignant astrocytoma (not otherwise specified)* NOTE: *Closed to accrual effective 5/28/2002 Progressive or recurrent disease confirmed by MRI or CT scan within the past 14 days Stable steroid dose for at least 5-7 days Confirmation of true progressive disease by PET scan, thallium scan, MR spectroscopy, or surgery if prior therapy included interstitial brachytherapy or stereotactic radiosurgery Failed prior radiotherapy Phase I (phase I completed effective 10/2/2001): No more than 2 prior chemotherapy or cytotoxic regimens, including 1 prior adjuvant therapy and 1 prior regimen for progressive or recurrent disease, or 2 prior regimens for progressive disease Phase II (phase II open only to patients requiring resection and who provide surgical tissue samples [effective 3/13/2003]): No more than 2 prior chemotherapy or cytotoxic regimens for relapsed disease following initial therapy (radiotherapy with or without chemotherapy) Prior surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks followed by another surgical resection is considered 1 relapse Patients who received prior therapy for a low-grade glioma with a surgical diagnosis of a high-grade glioma are considered to be in first relapse 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 2,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL (transfusion allowed) Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN Renal: Creatinine less than 1.5 mg/dL Cardiovascular: No uncontrolled high blood pressure No unstable angina No symptomatic congestive heart failure No myocardial infarction within the past 6 months No serious uncontrolled cardiac arrhythmia Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No severe nonmalignant systemic diseases or active infections No other severe concurrent disease that would preclude study therapy No allergy to azoles (e.g., ketoconazole, itraconazole, or voriconazole) HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior interferon No concurrent anticancer immunotherapy No concurrent routine prophylactic filgrastim (G-CSF) during first course of study No concurrent sargramostim (GM-CSF) Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, suramin, or mitomycin) At least 3 weeks since prior procarbazine At least 2 weeks since prior vincristine No other concurrent anticancer chemotherapy Endocrine therapy: See Disease Characteristics At least 1 week since prior tamoxifen Concurrent corticosteroids allowed No concurrent anticancer hormonal therapy Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered No concurrent anticancer radiotherapy Surgery: See Disease Characteristics At least 3 weeks since prior resection and recovered Prior recent resection of recurrent or progressive tumor allowed Other: Recovered from all prior therapy (excluding neurotoxicity or alopecia) Prior radiosensitizers allowed Concurrent H2 blockers and antacids allowed provided taken at least 2 hours before and after tipifarnib No concurrent proton pump inhibitors (e.g., omeprazole or lansoprazole) No other concurrent medication that would preclude study therapy (e.g., immunosuppressive agents) No other concurrent anticancer therapy No other concurrent investigational drugs No concurrent participation in any other clinical study No other concurrent medications except analgesics, chronic treatments for concurrent medical conditions, or agents for life-threatening medical problems
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy F. Cloughesy, MD
Organizational Affiliation
Jonsson Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1182
Country
United States
Facility Name
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0942
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Hillman Cancer Center at University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9154
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78284-6220
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16877733
Citation
Cloughesy TF, Wen PY, Robins HI, Chang SM, Groves MD, Fink KL, Junck L, Schiff D, Abrey L, Gilbert MR, Lieberman F, Kuhn J, DeAngelis LM, Mehta M, Raizer JJ, Yung WK, Aldape K, Wright J, Lamborn KR, Prados MD. Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study. J Clin Oncol. 2006 Aug 1;24(22):3651-6. doi: 10.1200/JCO.2006.06.2323.
Results Reference
result
PubMed Identifier
16170172
Citation
Cloughesy TF, Kuhn J, Robins HI, Abrey L, Wen P, Fink K, Lieberman FS, Mehta M, Chang S, Yung A, DeAngelis L, Schiff D, Junck L, Groves M, Paquette S, Wright J, Lamborn K, Sebti SM, Prados M. Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study. J Clin Oncol. 2005 Sep 20;23(27):6647-56. doi: 10.1200/JCO.2005.10.068.
Results Reference
result

Learn more about this trial

Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma

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