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

Adult Glioblastoma Clinical Trial

Official title:

A Phase I/II Trial of OSI-774 in Patients With Recurrent Malignant Gliomas and Malignant Gliomas Post Radiation Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00045110
• Other study ID #: NCI-2012-02490
• Secondary ID: NCI-2012-02490NC
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: September 6, 2002
• Last updated: July 9, 2014
• Start date: August 2002

Study information

• Verified date: July 2014
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

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. IV. Determine the 6-month progression-free survival, 12-month survival, and objective tumor response of patients treated with this drug.

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.

Other known NCT identifiers

• NCT00055276

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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
• Adult Mixed Glioma
• Astrocytoma
• Glioblastoma
• Glioma
• Gliosarcoma
• Meningioma
• Oligodendroglioma
• Recurrent Adult Brain Tumor

Intervention

Drug:
• erlotinib hydrochloride
Given orally

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	North American Brain Tumor Consortium	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) or erlotinib hydrochloride defined as the dose at which fewer than one-third of patients experience DLT (phase I)	Summarized by descriptive statistics.	28 days	Yes
Primary	Progression-free survival (phase II)		6 months	No
Secondary	Overall survival		At 1 year	No
Secondary	Response rate (complete or partial response) graded using RECIST criteria		At 1 year	No
Secondary	Toxicity described based on the CTC severity grading	Summarized by descriptive statistics.	Up to 1 year	Yes