Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over Pharmaceutical / Industry Perifosine 222 NCT00400920

Trial Description

Summary

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 progression-free survival rate after 6 months of treatment. Secondary goals include determination of molecular and metabolic effects of perifosine by tissue analysis and PET imaging.

Further Study Information

Only patients not taking EIAEDs will be considered for this study. If patients were previously on EIAEDs that have been discontinued, patients must have been off the agent for at least 2 weeks prior to registration. For patients who need to start an AED or the AED needs to be changed, it is strongly recommended that all efforts should be made to use a non-EIAED. If another non-EIAED cannot be used, the PI or co-PI should be notified immediately. Questions regarding these requirements should be discussed with PI or co-PI.

In addition, if cytoreductive surgery is recommended as part of the standard of care for tumor recurrence, all patients will be considered for the "surgical arm" of the trial. 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 and pharmacokinetic analyses. Ideally, tissue will be available from a prior surgical resection for intra-patient comparison. Following recovery from surgery, patients will restart perifosine until either tumor progression (as determined by brain imaging with CT or MRI every 2 months) or toxicity. All patients will be followed for overall survival after discontinuing perifosine. Biologic impact will also be determined by periodic PET imaging.

Following a diagnosis of tumor recurrence or progression, all patients will receive perifosine monotherapy until toxicity, progression, or death. Brain imaging (MRI/CT) will be performed at baseline and every 2 months (standard of care). PET imaging will be performed at baseline and every 4 months to assist with interpretation of tumor response. MR Spectroscopy and MR Perfusion may also be performed with every MRI to assist with interpretation of tumor response. Patients on the surgical arm trial will resume perifosine after recovering from surgery and continue until toxicity, progression, or death.

Eligibility Criteria

Inclusion Criteria:

• Patients must have shown unequivocal evidence for tumor progression by MRI or CT scan. Stable dose of steroids is not mandated for this study.

• 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 lapsed since prior radiation.

• Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT and bilirubin < 2.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL before starting therapy. These tests must be performed within 2 weeks prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion.

• Baseline MRI (with MR Perfusion if possible) must be performed within 2 weeks prior to treatment initiation.

• Baseline PET (dedicated study of the brain) must be performed within 2 weeks prior to treatment initiation.

• There is no limitation on the number of prior relapses or prior therapies.

• Patients must agree to practice adequate contraception. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration. Women must not be breast feeding.

• If cytoreductive surgery is planned for tumor recurrence at the time of enrollment, such patients are eligible for the surgical arm, taking perifosine for 5-10 days pre-operatively and then continuing perifosine after recovering from the effects of surgery.

• Measurable disease is not required for eligibility in patients who recently underwent resection as long as the following conditions are met as applicable:

• Progression of disease led to the surgery

• Gliadel wafers were not placed during the most recent surgery

• Neither convection enhanced delivery nor catheters for infusion of chemotherapy were used during the most recent surgery

• Radioactive seeds were not placed during the most recent surgery

• The histology of the most recent surgery documented recurrent/persistent/progressive malignant glioma Note, however, that patients who are eligible for surgery because of progressive disease may be considered for the surgical arm.

• Any adult patient with a recurrent/progressive malignant glioma is eligible. Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made.

• Patients must have shown unequivocal evidence for tumor progression by MRI or CT scan. Stable dose of steroids is not mandated for this study.

• 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 lapsed since prior radiation.

• Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver function (SGOT and bilirubin < 2.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL before starting therapy. These tests must be performed within 2 weeks prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion.

• Baseline MRI (with MR Perfusion if possible) must be performed within 2 weeks prior to treatment initiation.

• Baseline PET (dedicated study of the brain) must be performed within 2 weeks prior to treatment initiation.

• There is no limitation on the number of prior relapses or prior therapies.

• Patients must agree to practice adequate contraception. Women of childbearing potential must have a negative B-HCG pregnancy test documented within 7 days prior to registration. Women must not be breast feeding.

• If cytoreductive surgery is planned for tumor recurrence at the time of enrollment, such patients are eligible for the surgical arm, taking perifosine for 5-10 days pre-operatively and then continuing perifosine after recovering from the effects of surgery.

• Measurable disease is not required for eligibility in patients who recently underwent resection as long as the following conditions are met as applicable:

• Progression of disease led to the surgery

• Gliadel wafers were not placed during the most recent surgery

• Neither convection enhanced delivery nor catheters for infusion of chemotherapy were used during the most recent surgery

• Radioactive seeds were not placed during the most recent surgery

• The histology of the most recent surgery documented recurrent/persistent/progressive malignant glioma Note, however, that patients who are eligible for surgery because of progressive disease may be considered for the surgical arm.

• Any adult patient with a recurrent/progressive malignant glioma is eligible. Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade (malignant) glioma is made.

Exclusion Criteria:

• Patients must not be taking EIAEDs. If patients were previously on EIAEDs that have been discontinued, patients must have been off the agent for at least 2 weeks prior to registration.

• 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.

• Surgical arm only: Patients must not have received prior therapy with signal transduction inhibitors (including but not limited to ZD1839/gefitinib/Iressa, OSI-774/erlotinib/Tarceva, rapamycin/sirolimus, CCI-779/temsirolimus, STI-571/imatinib/Gleevec). Any questions about the eligibility based on prior treatments should be discussed with the PI or co-PI.

Trial Contact Information

Trial Lead Organizations/Sponsors

AOI Pharmaceuticals, Incorporated

Andrew B Lassman, MD

Principal Investigator

Online Collaborative Oncology Group		Ph: 415-946-2410
		Email: ocogtrials@ocog.net

U.S.A.
New York
	New York
	AOI Pharmaceuticals Investigative Site
		Lindsay Blair	Ph: 212-639-5762
		Andrew B Lassman, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00400920
Information obtained from ClinicalTrials.gov on April 08, 2008