Clinical and Molecular-Metabolic Phase II Trial of Perifosine for Recurrent/Progressive Malignant Gliomas

September 22, 2020 updated by: Memorial Sloan Kettering Cancer Center
The purpose of this study is to test the effectiveness of perifosine in preventing further tumor growth using the established optimal dose of the drug. A second goal is to determine if perifosine can block the molecules in the tumor that drive it to divide and grow.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase II study of the small molecule inhibitor perifosine (NSC 639966, D21266, KRX-0401) in the treatment of patients with recurrent glioblastoma multiforme (GBM) and other recurrent malignant gliomas. The goal of the phase II study is to determine efficacy as measured by the progressionfree survival rate after 6 months of treatment. Secondary goals include determination of molecular and metabolic effects of perifosine by tissue analysis and PET imaging.

In addition, when cytoreductive surgery is recommended as part of the standard of care at study entry, patients will be considered for a "surgical arm." In this case, patients will receive perifosine for 5-10 days before surgery during which tumor will be aliquoted both for diagnostic purposes and for molecular effects of the drug in vivo and for analysis of drug penetration into tumor tissue.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have shown unequivocal evidence for tumor progression by MRI or CT scan.
  • Patients must be on a stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI and PET scans.
  • Patients must have failed prior radiation therapy.
  • Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery (including gamma-knife or cyber-knife) must have confirmation of true progressive disease rather than radiation necrosis based upon either PET or Thallium scanning, and/or MR spectroscopy, and/or MR Perfusion, and/or surgical documentation of disease.
  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must have signed an authorization for the release of their protected health information.
  • Age > 18 years old, and with a life expectancy > 8 weeks.
  • Karnofsky Performance Status ≥ 50%
  • Patients must have recovered from all acute toxicities from prior therapies. At least 28 days must have elapsed since prior radiation.
  • Patients must have adequate bone marrow function
  • Patients must agree to practice adequate contraception.

Exclusion Criteria:

  • Patients must not be taking EIAEDs
  • Patients must not have any significant medical illnesses or other history that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
  • 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.
  • Patients must not have active infection or serious intercurrent medical illness.
  • HIV-Positive patients receiving combination anti-retroviral therapy are excluded from the study due to possible retro-viral drug interactions.
  • Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Following a diagnosis of tumor recurrence or progression, all patients will receive perifosine monotherapy until toxicity, progression, or death.
Drug: Perifosine

Dosing will be continuous, and for the purpose of this trial a cycle will be defined as 28 days. Perifosine will be given as a 600 mg loading dose on day 1. The loading dose will be divided into 4 equal doses of 150 mg each. The first 3 doses should be given with food in the adult day hospital to allow intravenous antiemetic prophylaxis, and 4th dose at bedtime at home. The interval between doses of perifosine should be no less than 4 hours. On day 2, patients will start the maintenance dose of 100 mg daily at bedtime at home.

In addition to baseline serum, all patients will have weekly serum drawn during weeks 2-4.

Other Names:
  • NSC 639966, D21266, KRX-0401

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the Efficacy of Perifosine in Patients With Recurrent/Progressive GBMs Not Taking EIAEDs as Measured by 6 Month Progression Free Survival/PFS.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine Metabolic Effects of Perifosine on Malignant Gliomas by PET Imaging
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Columbia University
University of Wisconsin, Madison
Keryx Biopharmaceuticals
Keryx / AOI Pharmaceuticals, Inc.
Online Collaborative Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2006

Primary Completion (Actual)

November 11, 2019

Study Completion (Actual)

November 11, 2019

Study Registration Dates

First Submitted

December 26, 2007

First Submitted That Met QC Criteria

December 26, 2007

First Posted (Estimate)

January 11, 2008

Study Record Updates

Last Update Posted (Actual)

October 19, 2020

Last Update Submitted That Met QC Criteria

September 22, 2020

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-044

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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