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CompletedNCT00025675Updated Jun 26, 2018

Gefitinib in Treating Patients With Recurrent or Progressive CNS Tumors

A Phase 2 interventional study of gefitinib in Brain and Central Nervous System Tumors, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Completed at 12 sites in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2018-06-26.

Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
105
Allocation
Non-randomized
Ages
18 Years to 120 Years
Sex
All
01

Study summary

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.

Read the detailed 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.

02

Conditions studied

  • Brain and Central Nervous System Tumors

Keywords

  • recurrent adult brain tumor
  • adult meningioma
  • adult glioblastoma
  • adult anaplastic astrocytoma
  • adult anaplastic oligodendroglioma
  • adult pilocytic astrocytoma
  • adult subependymoma
  • adult mixed glioma
  • adult meningeal hemangiopericytoma
  • adult grade III meningioma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • adult grade I meningioma
  • adult grade II meningioma
03

In context

Glioblastoma

1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.

This study's enrollment of 105 is above the median of 36 across 1,618 interventional studies indexed under Glioblastoma.

Browse Glioblastoma studies →

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.

Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
105 participants (actual)

Study arms

  • Active comparator
    p450

    p450 inhibitor

    Drug: gefitinib

  • Active comparator
    nonp450

    not on p450 inhibitor

    Drug: gefitinib

Interventions

  • Druggefitinib
06

What researchers measure

Primary outcomes

  1. Progression-free survival at 6 months

    Time frame: 6 months

07

Study locations

12 sites
  • Jonsson Comprehensive Cancer Center at UCLA
    Los Angeles, California 90095, United States
  • UCSF Comprehensive Cancer Center
    San Francisco, California 94143, United States
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
    Bethesda, Maryland 20892-1182, United States
  • NCI - Neuro-Oncology Branch
    Bethesda, Maryland 20892-8200, United States
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • University of Michigan Comprehensive Cancer Center
    Ann Arbor, Michigan 48109-0316, United States
  • Memorial Sloan-Kettering Cancer Center
    New York, New York 10021, United States
  • Hillman Cancer Center at University of Pittsburgh Cancer Institute
    Pittsburgh, Pennsylvania 15232, United States
  • Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
    Dallas, Texas 75390-9154, United States
  • M.D. Anderson Cancer Center at University of Texas
    Houston, Texas 77030-4009, United States
  • University of Texas Health Science Center at San Antonio
    San Antonio, Texas 78284-6220, United States
  • University of Wisconsin Comprehensive Cancer Center
    Madison, Wisconsin 53792, United States
08

References and documents

Publications

  • Norden AD, Raizer JJ, Abrey LE, Lamborn KR, Lassman AB, Chang SM, Yung WK, Gilbert MR, Fine HA, Mehta M, Deangelis LM, Cloughesy TF, Robins HI, Aldape K, Dancey J, Prados MD, Lieberman F, Wen PY. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol. 2010 Jan;96(2):211-7. doi: 10.1007/s11060-009-9948-7. Epub 2009 Jun 28. PubMed 19562255 ↗
  • Lassman AB, Rossi MR, Raizer JJ, Abrey LE, Lieberman FS, Grefe CN, Lamborn K, Pao W, Shih AH, Kuhn JG, Wilson R, Nowak NJ, Cowell JK, DeAngelis LM, Wen P, Gilbert MR, Chang S, Yung WA, Prados M, Holland EC. Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01. Clin Cancer Res. 2005 Nov 1;11(21):7841-50. doi: 10.1158/1078-0432.CCR-05-0421. Erratum In: Clin Cancer Res. 2006 Jan 1;12(1):322. Razier, Jeffrey R [corrected to Raizer, Jeffrey J]. PubMed 16278407 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 26, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00025675
Lead sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jan 27, 2003
Start date
Oct 9, 2001
Primary completion
Jul 5, 2006
Completion
Jan 2, 2010
Last update
Jun 26, 2018

Study contacts

Frank S. Lieberman, MD
study chair · University of Pittsburgh
View the source record on ClinicalTrials.gov ↗

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