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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Keryx Biopharmaceuticals
Keryx / AOI Pharmaceuticals, Inc.
Online Collaborative Oncology Group
University of Wisconsin, Madison
Columbia University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00590954
First received: December 26, 2007
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Malignant Gliomas
CNS
Brain Cancer
Cancer
Drug: Perifosine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical and Molecular-Metabolic Phase II Trial of Perifosine for Recurrent/Progressive Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Determine the efficacy of perifosine in patients with recurrent/progressive GBMs not taking EIAEDs as measured by 6mPFS. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine molecular effects of perifosine on AKT, RAS, and proliferation in malignant gliomas; Determine metabolic effects of perifosine on malignant gliomas by PET imaging; Identify molecular features that predict perifosine response. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 31
Study Start Date: May 2006
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: NSC 639966, D21266, KRX-0401

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590954

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Keryx Biopharmaceuticals
Keryx / AOI Pharmaceuticals, Inc.
Online Collaborative Oncology Group
University of Wisconsin, Madison
Columbia University
Investigators
Principal Investigator: Thomas Kaley, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00590954     History of Changes
Obsolete Identifiers: NCT00400920
Other Study ID Numbers: 06-044
Study First Received: December 26, 2007
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Malignant Gliomas
CNS
Brain Cancer
Cancer
Perifosine

Additional relevant MeSH terms:
Brain Neoplasms
Glioma
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 28, 2014