Perifosine and Torisel (Temsirolimus) for Recurrent/Progressive Malignant Gliomas
Pilot Trial of Temsirolimus and Perifosine in Recurrent/Progressive Malignant Gliomas
1 other identifier
interventional
10
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Dec 2014
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 29, 2014
CompletedFirst Posted
Study publicly available on registry
September 12, 2014
CompletedStudy Start
First participant enrolled
December 8, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 27, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 14, 2021
CompletedMay 25, 2023
May 1, 2023
2.9 years
August 29, 2014
May 23, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Clinical Benefit Rate
Clinical Benefit Rate is defined as the radiographic response rate plus 6-month progression-free survival (PFS) rate.
Up to 6 months from the start of treatment
Secondary Outcomes (1)
Median Overall Survival Rate
Up to 48 months from start of treatment
Study Arms (2)
Surgical Cohort - cytoreductive surgery
OTHERCytoreductive 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).
Medical Cohort - no cytoreductive surgery
OTHERNo-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).
Interventions
Standard of care/routine cytoreductive glioma resection surgery. Arm B only.
Perifosine is a pill that has not been approved by the FDA which blocks a messenger that tells cancer cells to grow.
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.
Eligibility Criteria
You may qualify if:
- 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
- Platelet count of at least 100,000/mm3 on at least 2 consecutive blood draws at least 1 week apart with results stable or trending upward
- Normal coagulation
- Cholesterol level \< or = 350 mg/dl and triglycerides level \< or = 400 mg/dl
- Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
- Women of childbearing potential must have a negative beta-human chorionic gonadotropin (B-hCG) pregnancy test documented within 7 days prior to treatment
- +10 more criteria
You may not qualify if:
- 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
- Uncontrolled intercurrent illness
- HIV-positive patients on combination antiretroviral therapy
- Other active concurrent malignancy
- History of gout which can be exacerbated by perifosine
- Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or perifosine
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Andrew B Lassman, MDlead
- Pfizercollaborator
- AEterna Zentariscollaborator
Study Sites (2)
Columbia University Irving Medical Center
New York, New York, 10032, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew B. Lassman, MD
Columbia University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Masking Details
- No Masking
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- John Harris Associate Professor of Neurology
Study Record Dates
First Submitted
August 29, 2014
First Posted
September 12, 2014
Study Start
December 8, 2014
Primary Completion
October 27, 2017
Study Completion
February 14, 2021
Last Updated
May 25, 2023
Record last verified: 2023-05
Data Sharing
- IPD Sharing
- Will not share