Imatinib Mesylate in Treating Patients With Recurrent Brain Tumor

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00049127
First received: November 12, 2002
Last updated: January 14, 2013
Last verified: December 2012
  Purpose

This phase I/II trial is studying the side effects and best dose of imatinib mesylate and to see how well it works in treating patients with a recurrent brain tumor that has not responded to previous surgery and radiation therapy. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth


Condition Intervention Phase
Adult Anaplastic Oligodendroglioma
Adult Mixed Glioma
Adult Oligodendroglioma
Recurrent Adult Brain Tumor
Drug: imatinib mesylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial Of Imatinib Mesylate; (Gleevec; STI571) In Treatment Of Recurrent Oligodendroglioma And Mixed Oligoastrocytoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of imatinib mesylate when given to patients who are receiving EIACs, defined as the highest safely tolerated dose level where, at most, 1 of 6 patients experiences DLT, graded according to CTCAE v4.0 (Phase I) [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
  • 6-month progression-free survival (PFS), defined as a patient being alive and progression-free 183 days after the date of registration (Phase II and Pilot) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 90% confidence interval estimated using the Duffy-Santner algorithm.


Secondary Outcome Measures:
  • Confirmed response (i.e., an objective status of CR, PR, or REGR on 2 successive evaluations at least 4 weeks apart after the start of study treatment) (Phase II and Pilot) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Percentage of patients progression-free (Phase II and Pilot) [ Time Frame: Time from study registration to date of disease progression or last follow-up, assessed up to 5 years ] [ Designated as safety issue: No ]
    The percentage of patient progression-free at 12 months, 18 months, and PFS will be estimated. Kaplan-Meier survival curves and logrank tests will be used to estimate progression-time distributions.

  • Overall time to death (Phase II and Pilot) [ Time Frame: Time from date of registration to date of death due to any cause or last follow-up, assessed up to 5 years ] [ Designated as safety issue: No ]
    Kaplan-Meier survival curves and logrank tests will be used to estimate survival distributions.

  • Quality of life as assessed by five Linear Analogue Self Assessment (LASA) items (Phase II and Pilot) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 93
Study Start Date: June 2003
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase II group 1
Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.
Drug: imatinib mesylate
Given orally
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Experimental: Phase II group 2
Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.
Drug: imatinib mesylate
Given orally
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent oligodendroglioma or mixed oligoastrocytoma who are currently on enzyme-inducing anticonvulsant therapy.

II. Determine the efficacy of imatinib mesylate, as measured by response, survival, and progression-free survival, in patients with recurrent oligodendroglioma or mixed oligoastrocytoma.

III. Compare pilot data of patients who have undergone > 2 prior chemotherapy regimens for recurrent, progressive, or mixed oligodendroglioma with traditional patients with recurrent or mixed oligodendroglioma.

IV. Determine the toxicity and safety of this drug in these patients. V. Correlate, preliminarily, 1p/19q alterations, alpha-PDFGR gene amplification, and levels of related downstream signaling elements in tumor tissue with clinical response in patients treated with this drug.

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II and a pilot study.

PHASE I: Patients receive oral imatinib mesylate twice daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate 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.

PHASE II:

GROUP 1 (CONCURRENT ENZYME-INDUCING ANTICONVULSANTS [EIACs]): Patients receive oral imatinib mesylate, at the MTD determined in phase I, twice daily for 4 weeks.

GROUP 2 (NON-EIACs): Patients receive oral standard-dose imatinib mesylate twice daily for 4 weeks.

In both groups, treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

PILOT STUDY: Patients are stratified and assigned to treatment groups as in phase II. Patients receive oral imatinib as in phase II.

Patients are followed every 2 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed oligodendroglioma or mixed oligoastrocytoma

    • Grade 2-4
    • Recurrent disease
  • Patients with mixed gliomas must have > 25% oligodendrogliomatous component
  • Failed prior surgery, radiotherapy, and temozolomide or nitrosourea-based therapy

    • Progressive disease by MRI or CT scan
  • Measurable or evaluable disease by MRI or CT scan
  • More than 2 prior chemotherapy regimens for progressive or recurrent disease (pilot study only)
  • Currently taking anticonvulsants which can induce cytochrome p450 (e.g., phenytoin, carbamazepine, barbiturates, or primidone (Phase I only)
  • No prior or concurrent significant intratumoral hemorrhage
  • Performance status - ECOG 0-2
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9 g/dL
  • Bilirubin no greater than 1.5 mg/dL
  • AST no greater than 3 times upper limit of normal
  • Creatinine no greater than 2.0 mg/dL
  • No myocardial infarction within the past 6 months
  • No congestive heart failure requiring maintenance therapy for life-threatening ventricular arrhythmias
  • No New York Heart Association class III or IV heart disease
  • No active uncontrolled infection
  • No other severe concurrent disease that would preclude study or interfere significantly with interpreting potential drug-induced toxic effects
  • No other active malignancy except nonmelanoma skin cancer
  • No concurrent serious immunocompromised status unless related to concurrent steroids
  • HIV-positive patients allowed
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study participation
  • At least 2 weeks since prior biologic noncytotoxic agents (e.g., thalidomide or interferon)
  • No concurrent biologic therapy or immunotherapy for brain cancer
  • No concurrent therapeutic warfarin or heparin

    • Low-dose warfarin and heparin (1 mg daily) allowed
  • No prior interstitial chemotherapy, including carmustine wafers, unless separate lesion seen on MRI outside of prior treatment field
  • At least 2 weeks since prior vincristine
  • At least 4 weeks since other prior chemotherapy (6 weeks for nitrosoureas)
  • No concurrent chemotherapy for brain cancer
  • At least 2 weeks since prior tamoxifen
  • Concurrent corticosteroids allowed if dose stable for at least 1 week prior to study entry
  • No concurrent hormonal therapy for brain cancer
  • At least 12 weeks since prior radiotherapy
  • No prior stereotactic radiosurgery or interstitial brachytherapy unless separate lesion seen on MRI outside of prior treatment field
  • No concurrent radiotherapy for brain cancer
  • No other concurrent investigational or noninvestigational therapy for brain cancer
  • At least 2 weeks since prior surgery for initial or progressive disease and recovered
  • No concurrent surgery for brain cancer
  • At least 2 weeks since prior isotretinoin
  • At least 4 weeks since prior investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049127

  Show 201 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Kurt Jaeckle North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049127     History of Changes
Other Study ID Numbers: NCI-2011-01576, N0272, U10CA025224, CDR0000257812
Study First Received: November 12, 2002
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Oligodendroglioma
Astrocytoma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2014