Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma

NCT00509431 | Completed Phase 1 DMC

• 2 other identifiers: CDR0000557423UCLA-0604104
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult mixed glioma; recurrent adult brain tumor; adult glioblastoma; adult pilocytic astrocytoma; adult diffuse astrocytoma; adult subependymal giant cell astrocytoma; adult oligodendroglioma

Outcome Measures

Primary Outcomes (1)

• To determine maximum tolerated dose and dose limiting toxicity of escalating doses of erlotinib in combination with sirolimus

  day 28 of cycle 1

Secondary Outcomes (2)

• To characterize the single-dose pharmacokinetic (PK) profile of erlotinib (in serum) and sirolimus (in whole blood) combination therapy in these patient populations

  Day 1 of cycle 1

• To characterize repeated-dose pharmacokinetic (PK) profile of erlotinib (in serum) and sirolimus (in whole blood) combination therapy in these patient populations

  Day 28 of cycle 1

Study Arms (1)

Erlotinib + Sirolimus

EXPERIMENTAL

This is an open-label,phase I single-arm dose-escalation and phase II study of continuous, once daily doses of erlotinib administered orally in combination with sirolimus in adult patients with malignant glioma at first, second or third recurrence

Drug: Erlotinib + Sirolimus

Interventions

Erlotinib + Sirolimus DRUG

In arm I of dose escalation phase,starting dose of erlotinib is 150 mg daily. Starting dose of sirolimus includes a 15 mg loading dose, followed by continuous dosing at 5 mg daily.Dose escalation will proceed according to protocol Phase II of the study was not conducted only Phase I

Erlotinib + Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed malignant glioma, including any of the following:
• Glioblastoma multiforme (GBM)
• Gliosarcoma (GS)
• Anaplastic astrocytoma (AA)
• Anaplastic oligodendroglioma (AO)
• Anaplastic mixed oligoastrocytomas (AMA)
• Malignant astrocytoma not otherwise specified (NOS)
• Prior low-grade glioma allowed provided there is histologic evidence of progression to a malignant glioma
• Must meet the following criteria for phase I:
• All types of malignant gliomas allowed
• No limitations on the number of relapses
• Must meet the following criteria for phase II:
• Only patients with GBM or GS are allowed
• Must be in first, second, or third relapse
• patients who had prior therapy (must include external beam radiotherapy) for a low-grade glioma that is considered standard, non-surgical treatment for a high-grade glioma, the surgical diagnosis of high-grade glioma will be considered the first relapse

You may not qualify if:

• Women who are pregnant or lactating
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or sirolimus
• Uncontrolled intercurrent illness including, but not limited to, any of the following:
• Ongoing or active infection requiring IV antibiotics
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Hyperlipidemia (e.g., grade 3 or greater hypercholesterolemia or hypertriglyceridemia) not controlled with medication
• Psychiatric illness or social situations that would limit compliance with study requirements
• Disorders associated with significant immunocompromise (e.g., HIV or systemic lupus erythematosus \[SLE\])
• Patients with another primary malignancy that has required treatment other than surgery within the past year (except for nonmelanoma skin cancer or carcinoma in situ)
• Patients with the inability to comply with the protocol requirements in the opinion of the investigator including those who can not take oral medications
• Patients who are unable to undergo routine imaging evaluations with magnetic resonance imaging scans
• Prior EGFR-directed or mTOR-directed therapies including sirolimus or sirolimus analogs
• Patients taking concurrent immunosuppressive agents other than prescribed corticosteroids

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Astrocytoma; Oligodendroglioma; Glioma; Brain Neoplasms

Interventions

Erlotinib Hydrochloride; Sirolimus

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Study Officials

• Timothy F. Cloughesy, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: July 31, 2007
• Study Start: August 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: September 1, 2012
• Last Updated: July 31, 2020

Record last verified: 2016-02

Locations

US (1)