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Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00005859
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 26, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE June 2, 2000
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date June 26, 2018
Actual Study Start Date  ICMJE May 16, 2000
Actual Primary Completion Date July 1, 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma
Official Title  ICMJE Phase I/II Trial of R115777 in Patients With Recurrent Malignant Glioma
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].)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE Drug: tipifarnib
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June¬†22,¬†2018)
136
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 1, 2006
Actual Primary Completion Date July 1, 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00005859
Other Study ID Numbers  ICMJE NABTC-9901
CDR0000067888 ( Registry Identifier: PDQ (Physician Data Query) )
U01CA062455 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Timothy F. Cloughesy, MD Jonsson Comprehensive Cancer Center
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP