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Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00045110
First received: September 6, 2002
Last updated: June 14, 2017
Last verified: June 2017
  Purpose
Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

Condition Intervention Phase
Adult Anaplastic Astrocytoma Adult Anaplastic Oligodendroglioma Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Adult Grade I Meningioma Adult Grade II Meningioma Adult Grade III Meningioma Recurrent Adult Brain Tumor Drug: erlotinib hydrochloride Other: laboratory biomarker analysis Other: pharmacological study Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of OSI-774 in Patients With Recurrent Malignant Gliomas and Malignant Gliomas Post Radiation Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I [ Time Frame: 28 days ]
    DLT Definition: any grade 3 thrombocytopenia and grade 4 anemia and neutropenia; any non-hematologic grade 3 toxicity; failure to recover from toxicities to be eligible for re-treatment with erlotinib within 2 weeks of the last dose of erlotinib.

  • Define Maximum Tolerated Dose (MTD) of Erlotinib by Phase 1 Cohorts [ Time Frame: cycle 1 - 28 days ]
    standard 3+3 dose escalation design 3 patients in each dose level, observed for 28 days before enrollment to next level. if none of the patients experienced DLT dose escalated, if 1 of 3 experienced DLT 3 more enrolled at that level, if none of the 3 additional pts had DLT escalate to next level, if one or more of the additional pts experienced DLT, the MTD was exceeded and 3 more patients were treated at the next lower dose (if only 3 pts treated at the lower dose). The MTD is the dose at which 0/3 or 1/6 patients have experienced a DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.

  • 6 Months Progression-free Survival in Recurrent Malignant Gliomas (Phase II) [ Time Frame: 6 months ]
    Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).


Secondary Outcome Measures:
  • Percent of Participants With a Grade 3 or 4 Adverse Events Phase 1 [ Time Frame: 1 year ]
    CTCAE

  • 1 Year Survival - Phase II Newly Diagnosed GBM Post RT [ Time Frame: At 1 year ]
    12 month survival for newly diagnosed stable GBM post RT treated with erlotinib post RT

  • Overall Survival Newly Diagnosed GBM Post RT [ Time Frame: 2 years ]
    Overall Survival defined as Time from Start of treatment to time of death due to any cause

  • Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II [ Time Frame: At 1 year ]

    Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI

    Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined.

    Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids.

    Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone.

    Stable/No Response: Does not qualify for CR, PR, or progression.

    Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).


  • Percent of Patients With One or More Grade 3-5 Toxicity Described Based on the CTC Severity Grading Phase II [ Time Frame: Up to 1 year ]
    Summarized by descriptive statistics.

  • Time of Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) - [ Time Frame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) - [ Time Frame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5 ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Estimation of the Area Under the Curve Per Dose Level Phase I (on Anticonvulsants) - [ Time Frame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5 ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Trough Level Per Dose Level Phase I (on Anticonvulsants) - [ Time Frame: cycle 1 day eight ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Peak Plasma Concentration Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg - [ Time Frame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5 ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Time to Peak Plasma Concentration for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg - [ Time Frame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5 ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Estimation of Area Under the Curve for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg- [ Time Frame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5 ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Trough Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg - [ Time Frame: One sample on day 8 cycle 1 ]
    plasma concentrations relative to erlotiniab administration and sample time and dose level

  • Pharmacokinetics (Plasma) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs [ Time Frame: Pre-surgery and time of resection ]
    Drug administered 6 days prior to surgery

  • Pharmacokinetics (Tissue) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs [ Time Frame: Pre-surgery and time of resection ]
    Drug administered 6 days prior to surgery


Enrollment: 136
Study Start Date: August 2002
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 Dose Escalation

Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

erlotinib hydrochloride given orally

Other: pharmacological study.

Drug: erlotinib hydrochloride
given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: pharmacological study
correlative studies
Experimental: Phase 2 recurrent malignant gliomas and nonprogressive GBM

Phase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose (150mg/day.

patients requiring surgery treated 7 days prior to tumor removal (150mg/day)

PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR)

erlotinib hydrochloride given orally

Other: pharmacological study, laboratory biomarker analysis.

Drug: erlotinib hydrochloride
given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Other: laboratory biomarker analysis
correlative studies
Other: pharmacological study
correlative studies

Detailed Description:

OBJECTIVES:

Phase 1 I. Determine the maximum tolerated dose of erlotinib in patients with recurrent malignant glioma or recurrent or progressive meningioma.

II. Determine the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.

Phase 2 I. Determine the 6-month progression-free survival (recurrent malignant glioma) II.12-month survival of patients treated with this drug (stable glioblastoma post radiation therapy)

Phase 2 - Secondary Recurrent Malignant Glioma I. Objective Tumor Response rate associated with erlotinib therapy in recurrent or progressive malignant glioma.

III. 12-month survival of patients treated with this drug Determine the safety profile of this drug in these patients. IV.. Determine the pharmacokinetics of this drug in these patients

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to study phase (I vs II), concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no), histology (recurrent GBM vs recurrent anaplastic glioma vs recurrent meningioma vs stable GBM), preoperative candidacy (yes vs no), and concurrent steroids (yes vs no).

Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Once the MTD is determined, additional patients concurrently receiving EIAEDs are treated with erlotinib as above at the phase II dose. Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose.

Patients are followed for survival.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • One of the following diagnoses:

    • Histologically confirmed intracranial malignant glioma

      • Glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant astrocytoma not otherwise specified
      • Original histology of low-grade glioma allowed provided a subsequent histology of malignant glioma is confirmed
    • Histologically or radiographically confirmed recurrent or progressive benign or malignant meningioma
  • Progressive disease or tumor recurrence on MRI or CT scan

    • Phase I: No more than 3 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
    • Phase II: No more than 2 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
  • Patients with progressive disease must have failed prior radiotherapy* that was completed at least 4 weeks ago

    • Patients with progressive disease between 4 and 12 weeks after completion of external beam radiotherapy must have clear evidence of progression on MRI
    • Patients with GBM who have completed external beam radiotherapy and do not show progression are eligible
    • Patients with progressive disease after interstitial brachytherapy or stereotactic radiosurgery must have confirmed true progression rather than radiation necrosis based upon positron-emission tomography, thallium scanning, MRI, or surgical documentation
  • Measurable or evaluable disease
  • Performance status - Karnofsky 60-100%
  • More than 8 weeks
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 mg/dL (transfusion allowed)
  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • SGOT less than 1.5 times ULN
  • Creatinine less than 1.5 mg/dL
  • None of the following ophthalmic abnormalities:

    • Abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
    • Congenital abnormality (e.g., Fuch's dystrophy)
    • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
    • Abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Patients found to have dry eyes on examination but have an otherwise normal examination allowed
  • No active infection
  • No other serious concurrent medical illness
  • No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No other disease that would obscure toxicity or dangerously alter drug metabolism
  • No significant medical illness that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 12 weeks after study participation
  • See Disease Characteristics
  • At least 1 week since prior thalidomide
  • At least 1 week since prior interferon
  • At least 4 weeks since prior SU5416 or other experimental biologic agents
  • See Disease Characteristics
  • No prior chemotherapy (including polifeprosan 20 with carmustine implant [Gliadel wafers]) for patients with stable GBM
  • At least 2 weeks since prior vincristine
  • At least 3 weeks since prior procarbazine
  • At least 6 weeks since prior nitrosoureas
  • At least 1 week since prior tamoxifen
  • See Disease Characteristics
  • Recovered from prior radiotherapy
  • No more than 6 weeks since prior external beam radiotherapy for patients with GBM without evidence of progression
  • Recovered from prior surgery
  • Recovered from prior therapy
  • At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) except radiosensitizers
  • At least 4 weeks since prior cytotoxic therapy
  • At least 4 weeks since prior tipifarnib or imatinib mesylate
  • No prior erlotinib or other epidermal growth factor receptor inhibitors
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  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: NCT00045110

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
University of California San Francisco
San Francisco, California, United States, 94115
United States, Maryland
National Cancer Institute Neuro-Oncology Branch
Bethesda, Maryland, United States, 20814
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75235
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Lauren Abrey, MD National Cancer Institute (NCI)
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00045110     History of Changes
Obsolete Identifiers: NCT00055276
Other Study ID Numbers: NCI-2012-02490
NCI-2012-02490 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-03-C-0114
CDR0000256358
NABTC-01-03 ( Other Identifier: North American Brain Tumor Consortium )
NABTC-01-03 ( Other Identifier: CTEP )
U01CA062399 ( U.S. NIH Grant/Contract )
Study First Received: September 6, 2002
Results First Received: May 4, 2017
Last Updated: June 14, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Gliosarcoma
Oligodendroglioma
Meningioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Vascular Tissue
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Erlotinib Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 16, 2017