Temsirolimus and Perifosine in Treating Patients With Recurrent or Progressive Malignant Glioma

NCT01051557 | Completed Phase 1 Results

• 7 other identifiers: NCI-2011-0140909-058MSKCC-09058CDR00006635738249P30CA008748U01CA069856
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of temsirolimus when given together with perifosine and to see how well it works in treating patients with recurrent or progressive malignant glioma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as perifosine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with perifosine may be an effective treatment for malignant glioma.

Conditions

Adult Anaplastic Astrocytoma; Adult Anaplastic Oligodendroglioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Temsirolimus

  MTD defined as the dose at which fewer than one-third of patients experience a dose limiting toxicity (DLT) according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I)

  28 days

• Determine the Efficacy of Temsirolimus in Combination With Perifosine in Patients With Recurrent/Progressive Glioblastomas (GBMs) Not Taking EIAEDs as Measured by 6 Month Progression-free Survival (6mPFS) and Radiographic Response Rates. (Phase II)

  5 years

Study Arms (1)

Treatment (temsirolimus and perifosine)

EXPERIMENTAL

PHASE I: Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and perifosine PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients receive temsirolimus and perifosine as in phase I. Some patients may also undergo cytoreductive surgery.

Other: Laboratory Biomarker Analysis; Drug: Perifosine; Drug: Temsirolimus; Procedure: Therapeutic Conventional Surgery

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (temsirolimus and perifosine)

Perifosine DRUG

Given PO

Also known as: 4-[[Hydroxy(octadecyloxy)phosphinyl]oxy]-1,1-dimethylpiperidinium, Inner Salt, D21266, Octadecylphosphopiperidine

Treatment (temsirolimus and perifosine)

Temsirolimus DRUG

Given IV

Also known as: CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel

Treatment (temsirolimus and perifosine)

Therapeutic Conventional Surgery PROCEDURE

Undergo cytoreductive surgery

Treatment (temsirolimus and perifosine)

Eligibility Criteria

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

You may qualify if:

• Patients must have unstained slides or tissue blocks available from at least one prior surgery; frozen tissue is also requested if available
• Patients must have received prior radiotherapy and temozolomide; there is otherwise no limit on the number of prior recurrences/therapies
• At least 6 weeks (42 days) must have elapsed since completion of radiation therapy to initiation of study treatment
• At least 4 weeks (28 days) must have elapsed since most recent temozolomide and initiation of study treatment
• Patients must have recovered from the toxic effects of other prior direct inhibitors of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR): 4 weeks from prior therapy with agents such as bevacizumab (Avastin), aflibercept (VEGF-Trap), cediranib (AZD2171), or XL-184 (BMS 907351); any questions regarding the definition of a direct anti-VEGF/VEGFR therapy must be discussed with the principal investigator (PI) or co-PI; patients must have recovered from the toxic effects of other prior therapy including: 4 weeks (28 days) from any investigational agent, two weeks (14 days) from vincristine, 6 weeks (42 days) from nitrosoureas, 3 weeks (21 days) from procarbazine administration, and 1 week (7 days) for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count), and 4 weeks (28 days) from any other prior cytotoxic therapy; any questions related to the definition of non-cytotoxic agents should be directed to the co-PI
• Patients must have shown unequivocal evidence for tumor progression by magnetic resonance imaging (MRI)/computed tomography (CT) on the baseline MRI/CT in comparison to a prior scan OR have recently undergone resection for recurrent/progressive disease; the baseline brain MRI/CT must be performed 14 days or fewer prior to treatment; the same type of scan, i.e., MRI (or CT for patients who cannot undergo MRI) must be used throughout the period of protocol treatment for tumor measurement; criteria for progression on this study are not mandatory if the disease progression is obvious in the opinion of the investigator; any questions should be addressed to the PI
• Patients must be on a stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI/CT (and positron emission tomography \[PET\] scans for patients on the phase II study) except patients undergoing surgery on the surgical substudy of phase II; if the corticosteroid dose is increased between the date of imaging and registration a new baseline MR/CT is required
• Karnofsky performance status \>= 60%
• Life expectancy of greater than 8 weeks
• White blood cell (WBC) \>= 2,000/ul
• Absolute neutrophil count (ANC) \>= 1,500/mm\^3
• Platelet count of \>= 100,000/mm\^3
• Platelet count of at least 100,000/mm\^3 on at least 2 consecutive blood draws, at least 1 week apart, with results stable/trending upward; any question regarding the definition of stable/trending upward must be discussed with the PI
• Hemoglobin \>= 10 gm/dl; eligibility level for hemoglobin may be reached by transfusion
• Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) \< 2 times upper limit of normal (ULN)

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus or perifosine
• Patients must not be taking EIAED; if previously on an EIAED, the patient must be off of it for at least two weeks prior to treatment on study
• Patients must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with temsirolimus and perifosine
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• PHASE II: Patients may not have received prior treatment with mTOR inhibitors such as temsirolimus, rapamycin (sirolimus), or RAD001 (everolimus); any question regarding the definition of mTOR inhibiting therapy must be discussed with the PI; such prior therapy is allowed for the phase I component
• PHASE II: Patients may not have previously received perifosine or other AKT targeting agents; any question regarding the definition of AKT targeting therapy must be discussed with the PI; such prior therapy is allowed for the phase I component
• PHASE II: Patients must not have received prior treatment with convection enhanced delivery, other catheter based intra-tumoral treatment, or carmustine (BCNU)/Gliadel wafers; such prior therapy is allowed for the phase I component
• PHASE II: Patients with prior therapy that included stereotactic radiosurgery (including gamma-knife or cyber-knife) during therapy for newly diagnosed or recurrent disease, or re-irradiation of any type, must have confirmation of true progressive disease rather than radiation necrosis based upon surgical documentation of recurrent/progressive disease; imaging with magnetic resonance (MR) spectroscopy, PET, or other techniques is not adequate to exclude radiation necrosis for this study; such prior therapy is allowed for the phase I component and does not require surgical documentation of disease
• PHASE II: Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible for the phase II study but are eligible for the phase I component

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

perifosine; octadecyl-(N,N-dimethylpiperidino-4-yl)-phosphate; temsirolimus; Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Thomas Kaley
• Organization: Memorial Sloan Kettering Cancer Center

kaleyt@mskcc.org

212-639-5122

Study Officials

• Thomas J Kaley

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 18, 2010
• Study Start: January 27, 2010
• Primary Completion: November 16, 2018
• Study Completion: September 30, 2020
• Last Updated: July 19, 2021
• Results First Posted: April 18, 2016

Record last verified: 2021-06

Locations

US (1)