Brain Cancer, Cancer, CNS, Malignant Gliomas
Conditions
Keywords
Malignant Gliomas, CNS, Brain Cancer, Cancer, Perifosine
Brief summary
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.
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.
Interventions
DRUGPerifosine
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.
Sponsors
Keryx Biopharmaceuticals
Keryx / AOI Pharmaceuticals, Inc.
Online Collaborative Oncology Group
University of Wisconsin, Madison
Columbia University
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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. | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Determine Metabolic Effects of Perifosine on Malignant Gliomas by PET Imaging | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Following a diagnosis of tumor recurrence or progression, all patients will receive perifosine monotherapy until toxicity, progression, or death.
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. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Inevaluable | 2 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Continuous | 51 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 32 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 32 |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 22 / 32 |
Outcome results
Primary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glioblastoma | Determine the Efficacy of Perifosine in Patients With Recurrent/Progressive GBMs Not Taking EIAEDs as Measured by 6 Month Progression Free Survival/PFS. | 1.58 months |
| Anaplastic Glioma | Determine the Efficacy of Perifosine in Patients With Recurrent/Progressive GBMs Not Taking EIAEDs as Measured by 6 Month Progression Free Survival/PFS. | 2.12 months |
Secondary
Determine Metabolic Effects of Perifosine on Malignant Gliomas by PET Imaging
Time frame: 2 years
Population: Data were not collected