Pilot Trial of Temsirolimus and Perifosine in Recurrent/Progressive Malignant Gliomas

Andrew B Lassman, MD2 sites in 1 country10 target enrollmentDecember 8, 2014

ConditionsBrain Tumor, Recurrent Glioblastoma Anaplastic Astrocytoma Anaplastic Oligodendroglioma Mixed Glioma

InterventionsCytoreductive surgery Perifosine Temsirolimus

DrugsPerifosine Temsirolimus

Overview

Phase: Phase 1
Intervention: Cytoreductive surgery
Conditions: Brain Tumor, Recurrent
Sponsor: Andrew B Lassman, MD
Enrollment: 10
Locations: 2
Primary Endpoint: Clinical Benefit Rate
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to test the effectiveness of a drug called temsirolimus in combination with a drug called perifosine in treating brain tumors that have continued to grow after previous treatment. Temsirolimus is an intravenous drug approved by the FDA for treatment of other cancers (kidney cancer, certain types of lymphoma) but not for brain tumors. Perifosine is a pill that has not been approved by the FDA which blocks a messenger that tells cancer cells to grow. Research suggests that combined treatment with both drugs is better than either alone, and that it is reasonably safe.

Detailed Description

Malignant gliomas are the most common primary brain tumors, and glioblastoma (GBM) is the most common subtype in adults, representing more than 50% of gliomas. Standard initial treatment for newly diagnosed GBM consists of maximal surgical resection followed by radiotherapy to the tumor bed and chemotherapy with an oral DNA alkylator, temozolomide. However, recurrence is nearly universal despite standard therapy. There is no standard treatment at recurrence. Median survival is about 15 months from diagnosis and 6 months from recurrence. Once patients develop tumor progression, conventional chemotherapy is generally ineffective.

Registry

clinicaltrials.gov

Start Date

December 8, 2014

End Date

February 14, 2021

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Andrew B Lassman, MD

Responsible Party

Sponsor Investigator

Principal Investigator

Andrew B Lassman, MD

John Harris Associate Professor of Neurology

Columbia University

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed intracranial glioblastoma (GBM), including sub variants
•At least 15 unstained slides or at least 1 tissue blocks must be collected from at least one prior surgery.
•Received prior radiotherapy and prior temozolomide as treatment for the malignant glioma
•Recovered from toxic effects of prior therapies and at least 2 weeks must have elapsed since any prior signaling pathway modulators; in general, at least 4 weeks must have elapsed from any other anticancer therapy
•Able to undergo contrast enhanced magnetic resonance imaging (MRI) scans or CT scans
•Shown unequivocal evidence for contrast enhancing tumor progression by MRI or CT in comparison to a prior scan
•Age \> or = 18 years
•Karnofsky Performance Status \> or = 70
•Life expectancy of \> 8 weeks
•Normal organ and marrow function, adequate liver function, and adequate renal function before starting therapy

Exclusion Criteria

•There is no limit on the number or type of prior chemotherapies except:
•convection enhanced delivery, catheter based intra-tumoral treatment, or carmustine (BCNU)/Gliadel® wafers
•stereotactic radiosurgery, or re-irradiation of any type
•agent designed to inhibit mTOR or PI3K/AKT
•direct Vascular Endothelial Growth Factor (VEGF)/Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitors
•Smoking or plan to smoke tobacco or marijuana during study therapy
•Plan to eat grapefruit or drink grapefruit juice during study therapy
•Receiving any other investigational agents concurrently with study treatment
•Taking hepatic Enzyme Inducing Anti-Epileptic Drug (EIAED)
•Taking medications that are inducers or inhibitors of Cytochrome P450 3A4 (CYP3A4) for at least two weeks prior to study treatment

Arms & Interventions

Surgical Cohort - cytoreductive surgery

Cytoreductive surgery planned (surgical cohort). After post-operative standard evaluations, patients will resume therapy. After anti-emetic prophylaxis, patients will receive the first divided dose of the perifosine loading dose after recovery from surgery. Patients will be observed for at least 30 minutes to ensure there has been adequate anti-emetic prophylaxis, and then patients will receive temsirolimus administered over 30-60 minutes IV. The remaining divided doses of the perifosine loading dose will then be administered. Patients will then return weekly for infusion of temsirolimus over 30-60 minutes IV. Dosing will be continuous although for the purposes of evaluation, a cycle will be defined as 4 weeks (28 days).

Intervention: Cytoreductive surgery

Surgical Cohort - cytoreductive surgery

Intervention: Perifosine

Surgical Cohort - cytoreductive surgery

Intervention: Temsirolimus

Medical Cohort - no cytoreductive surgery

No-Cytoreductive surgery planned (medical cohort). After anti-emetic prophylaxis, patients will receive the first divided dose of the perifosine loading dose. Patients will be observed for at least 30 minutes to ensure there has been adequate anti-emetic prophylaxis, and then patients will receive temsirolimus administered over 30-60 minutes IV. The remaining divided doses of the perifosine loading dose will then be administered. Patients will then return weekly for infusion of temsirolimus over 30-60 minutes IV. Dosing will be continuous although for the purposes of evaluation, a cycle will be defined as 4 weeks (28 days).

Intervention: Perifosine