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Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

Phase I/II Trial of STI571 (NSC 716051) in Patients With Recurrent Malignant Gliomas


OBJECTIVES:

- Determine the maximum tolerated dose of imatinib mesylate in patients with recurrent
malignant glioma or meningioma.

- Determine the safety profile of this drug in these patients.

- Determine the pharmacokinetics of this drug, with or without concurrent enzyme-inducing
anti-epileptic drugs (EIAEDs), in these patients. (Stratum of patients currently taking
EIAEDs closed to accrual as of 05/15/2003 for phase I and phase II)

- Determine angiogenic activity in vivo using functional neuro-imaging studies and in
vitro with assays of serum angiogenic peptides.

- Determine the efficacy of this drug, in terms of 6-month progression-free survival and
objective tumor response, in these patients.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to
concurrent enzyme-inducing anti-epileptic drug use (yes [stratum closed to accrual as of
05/15/2003 for phase I and phase II] vs no).

- Phase I (patients with glioma or meningioma) Patients in cohorts 1 and 2 receive oral
imatinib mesylate (STI571) once daily on days 1-28. Patients in cohorts 3-5 receive
oral STI571 twice daily on days 1 and 3-28 of the first course and on days 1-28 of
subsequent courses. Courses repeat every 4 weeks in the absence of disease progression
or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of STI571 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 (patients with glioma) (glioblastoma multiforme patients excluded as of
05/15/2003) Patients receive oral STI571 at the MTD determined in phase I, 1-2 times
daily for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression
or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for phase I of the study within 6
months and a total of 39 patients will be accrued for phase II of the study within 6-8
months. (Glioblastoma multiforme patients excluded from phase II as of 05/13/2003).

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed recurrent or unresectable malignant glioma

- Glioblastoma multiforme (phase I only)

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Malignant astrocytoma not otherwise specified

- Gliosarcoma

- Low-grade histology with subsequent diagnosis of malignant glioma allowed (phase
I only) OR

- Histologically confirmed recurrent or unresectable benign or malignant meningioma
(phase I only)

- No prior intracranial hemorrhage

- Failed prior radiotherapy

- Progressive or recurrent disease by MRI or CT scan and/or resection

- PET or thallium scan, MR spectroscopy, or surgical documentation required in
patients who have received prior interstitial brachytherapy or stereotactic
radiosurgery

- Stable dose of steroids for 5-7 days prior to MRI or CT scan

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- More than 8 weeks

Hematopoietic:

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

- Bilirubin less than 2 times upper limit of normal (ULN)

- SGOT less than 2 times ULN

- No significant hepatic disease

Renal:

- Creatinine less than 1.5 mg/dL

- Creatinine clearance at least 60 mL/min

- No significant renal disease

Cardiovascular:

- No significant cardiac disease

- No deep venous or arterial thrombosis within the past 6 weeks

Pulmonary:

- No pulmonary embolism within the past 6 weeks

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for up to 6
months after study participation

- No other serious concurrent medical illness

- No serious active infection

- No concurrent disease that would obscure toxicity or alter drug metabolism

- No other malignancy within the past 3 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 1 week since prior interferon or thalidomide and recovered

- No concurrent immunotherapy

- No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy:

- Recovered from prior chemotherapy

- At least 4 weeks since prior cytotoxic therapy

- At least 2 weeks since prior vincristine

- At least 6 weeks since prior nitrosoureas

- At least 4 weeks since prior temozolomide

- At least 3 weeks since prior procarbazine

- Prior polifeprosan 20 with carmustine implant (Gliadel wafer) allowed

- Prior radiosensitizers allowed

- No other concurrent chemotherapy

- Phase I only:

- Prior chemotherapy required for anaplastic astrocytoma, anaplastic
oligodendroglioma, and anaplastic mixed oligoastrocytoma

- Prior treatment for up to 3 relapses allowed

- Phase II only:

- Prior chemotherapy not required

- Prior treatment for up to 2 relapses allowed

Endocrine therapy:

- See Disease Characteristics

- At least 1 week since prior tamoxifen and recovered

- No concurrent anticancer hormonal therapy

Radiotherapy:

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy

- No concurrent radiotherapy

Surgery:

- See Disease Characteristics

- Recovered from prior surgical resection of recurrent or progressive disease

Other:

- At least 1 week since prior non-cytotoxic agents and recovered

- At least 1 week since prior tretinoin and recovered

- At least 2 weeks since prior drugs that affect hepatic metabolism

- No other concurrent investigational agents

- No concurrent warfarin

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Patrick Y. Wen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000068437

NCT ID:

NCT00010049

Start Date:

November 2002

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult meningioma
  • adult glioblastoma
  • adult anaplastic astrocytoma
  • adult anaplastic oligodendroglioma
  • adult mixed glioma
  • adult pilocytic astrocytoma
  • adult subependymoma
  • adult grade III meningioma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioma
  • Meningioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Hillman Cancer Center at University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15236
Simmons Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390-9063
Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182