Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

Johns Hopkins Medicine

Status and phase

Completed

Phase 2

Conditions

Brain and Central Nervous System Tumors

Treatments

Drug: gefitinib

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00025675

U01CA062399 (U.S. NIH Grant/Contract)

NABTC-0001

ABTC-0001

NABTC-0001 CDR0000068984

Details and patient eligibility

About

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of CNS tumors.

PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have recurrent or progressive CNS tumors.

Full description

OBJECTIVES:

Determine the maximum tolerated dose of gefitinib in patients with recurrent or progressive supratentorial malignant gliomas or brain or spinal meningiomas receiving enzyme-inducing antiepileptic drugs (EIAEDs). (Phase I of the study closed to accrual as of 09/19/2003).
Determine the toxic effects of this drug in these patients.
Determine the pharmacokinetics of this drug in patients receiving EIAEDs.
Determine the efficacy of this drug in terms of 6-month progression-free survival of these patients.
Determine the safety profile of the phase II dose of this drug in these patients.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no) and disease type (for phase II only) (benign meningioma vs malignant meningioma vs hemangiopericytoma vs glioblastoma vs other anaplastic glioma). (Phase I closed to accrual as of 09/19/2003).

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients (who are receiving EIAEDs) receive escalating doses of gefitinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 2 weeks.

PROJECTED ACCRUAL: A minimum of 30 patients will be accrued for the phase I portion of this study within 10 months . (Phase I closed to accrual as of 09/19/2003). A total of 48 patients will be accrued for the phase II portion of this study within 6-8 months.

Enrollment

105 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Histologically confirmed supratentorial malignant primary glioma
  - Glioblastoma multiforme
  - Anaplastic astrocytoma
  - Anaplastic oligodendroglioma
  - Anaplastic mixed oligoastrocytoma
  - Malignant astrocytoma not otherwise specified
- Histologically confirmed or radiographically defined recurrent or progressive brain or spinal meningioma, including base of skull or cavernous sinus meningiomas
  - Benign, malignant, or atypical
  - May include neurofibromatosis type I or II
  - Hemangiopericytoma allowed
Recurrent or progressive disease by MRI or CT scan
- Evidence of true progressive disease by PET or thallium scan, MR spectroscopy, or surgical documentation required if patient received prior interstitial brachytherapy or stereotactic radiosurgery (to the target lesion for meningioma and hemangiopericytoma)
- Steroid dosage must be stable for at least 5 days prior to scan
No limitations on the number of prior surgeries, radiotherapy or chemotherapy regimens, or radiosurgery treatments for patients with meningioma or hemangiopericytoma and may include standard external beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery in any combination
Patients with glioma must have failed prior radiotherapy
Original histology of low-grade glioma allowed if subsequent confirmation of malignant glioma is made at time of recurrence
Phase I (closed to accrual as of 09/19/2003):
- Prior treatment for no more than 3 prior relapses in patients with glioma
Phase II:
- Measurable disease after prior surgical resection of recurrent or progressive disease
- Prior treatment for no more than 2 prior relapses in patients with glioma

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 1,500/mm^3
Platelet count at least 120,000/mm^3
Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic:

Bilirubin less than 1.5 times upper limit of normal (ULN)
SGOT less than 1.5 times ULN

Renal:

Creatinine less than 1.5 mg/dL OR
Creatinine clearance at least 60 mL/min

Cardiovascular:

No significant cardiac risk factors within the past 6 months

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No gastrointestinal risk factors (e.g., active ulcerative colitis) within the past 6 months
No active infection
No concurrent disease that would obscure toxicity or dangerously alter drug metabolism
No other significant medical illness that would preclude study
No other malignancy within the past 3 years except non-melanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior interferon or thalidomide
No concurrent filgrastim (G-CSF)

Chemotherapy:

See Disease Characteristics
At least 2 weeks since prior vincristine
At least 6 weeks since prior nitrosoureas
At least 3 weeks since prior procarbazine

Endocrine therapy:

At least 1 week since prior tamoxifen

Radiotherapy:

See Disease Characteristics
At least 4 weeks since prior radiotherapy

Surgery:

See Disease Characteristics
At least 7 days since prior surgery for recurrent or progressive tumor and recovered

Other:

Recovered from prior therapy
No prior gefitinib or other epidermal growth factor receptor inhibitor
At least 1 week since prior isotretinoin
At least 1 week since other prior noncytotoxic agents (except radiosensitizers)
At least 4 weeks since prior investigational agents
Concurrent low-molecular weight heparin or warfarin for deep vein thrombosis or pulmonary embolism allowed