Clinical trial NCT00045110: Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma
Official title: A Phase I/II Trial of OSI-774 in Patients With Recurrent Malignant Gliomas and Malignant Gliomas Post Radiation Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I
timeFrame: 28 days
measure: Define Maximum Tolerated Dose (MTD) of Erlotinib by Phase 1 Cohorts
timeFrame: cycle 1 - 28 days
measure: 6 Months Progression-free Survival in Recurrent Malignant Gliomas (Phase II)
timeFrame: 6 months
Secondary outcomes:
measure: Percent of Participants With a Grade 3 or 4 Adverse Events Phase 1
timeFrame: 1 year
measure: 1 Year Survival - Phase II Newly Diagnosed GBM Post RT
timeFrame: At 1 year
measure: Overall Survival Newly Diagnosed GBM Post RT
timeFrame: 2 years
measure: Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II
timeFrame: At 1 year
measure: Percent of Patients With One or More Grade 3-5 Toxicity Described Based on the CTC Severity Grading Phase II
timeFrame: Up to 1 year
measure: Time of Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -
timeFrame: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1.
measure: Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -
timeFrame: 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
measure: Estimation of the Area Under the Curve Per Dose Level Phase I (on Anticonvulsants) -
timeFrame: 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
measure: Trough Level Per Dose Level Phase I (on Anticonvulsants) -
timeFrame: cycle 1 day eight
measure: Peak Plasma Concentration Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -
timeFrame: 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
measure: Time to Peak Plasma Concentration for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -
timeFrame: 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
measure: Estimation of Area Under the Curve for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg-
timeFrame: 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
measure: Trough Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -
timeFrame: One sample on day 8 cycle 1
measure: Pharmacokinetics (Plasma) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs
timeFrame: Pre-surgery and time of resection
measure: Pharmacokinetics (Tissue) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs
timeFrame: Pre-surgery and time of resection
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Bethesda
country: United States
facility: National Cancer Institute Neuro-Oncology Branch
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: National Cancer Institute (NCI)
name: Lauren Abrey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raizer JJ, Abrey LE, Lassman AB, Chang SM, Lamborn KR, Kuhn JG, Yung WK, Gilbert MR, Aldape KD, Wen PY, Fine HA, Mehta M, Deangelis LM, Lieberman F, Cloughesy TF, Robins HI, Dancey J, Prados MD; North American Brain Tumor Consortium. A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas. Neuro Oncol. 2010 Jan;12(1):87-94. doi: 10.1093/neuonc/nop017. Epub 2009 Dec 14.