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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00590954
• Collaborator: Keryx Biopharmaceuticals (Industry), Keryx / AOI Pharmaceuticals, Inc. (Industry), Online Collaborative Oncology Group (Other), University of Wisconsin, Madison (Other), Columbia University (Other)
• Enrollment: 32
• Location: 1
• Arm: 1
• Actual Duration (Months): 162.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Gliomas; CNS; Brain Cancer; Cancer	Drug: Perifosine	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical and Molecular-Metabolic Phase II Trial of Perifosine for Recurrent/Progressive Malignant Gliomas
• Actual Study Start Date: May 1, 2006
• Actual Primary Completion Date: Nov 11, 2019
• Actual Study Completion Date: Nov 11, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Determine Metabolic Effects of Perifosine on Malignant Gliomas by PET Imaging [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 25, 2011

More Information

Additional Information:

• Memorial Sloan-Kettering web site

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00590954
• Other Study ID Numbers: 06-044; NCT00400920
• First Posted: Jan 11, 2008
• Last Update Posted: Oct 19, 2020
• Last Verified: Nov 1, 2019

• Keywords provided by Memorial Sloan Kettering Cancer Center: Malignant Gliomas; CNS; Brain Cancer; Cancer; Perifosine
• Additional relevant MeSH terms: Glioma; Brain Neoplasms

Study Results

Participant Flow

Arm/Group Title	Treatment
Arm/Group Description	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.
Period Title: Overall Study
STARTED	32
COMPLETED	30
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment
Arm/Group Description	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.
Overall Participants	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51
Sex: Female, Male (Count of Participants)
Female	15 46.9%
Male	17 53.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.3%
Not Hispanic or Latino	30 93.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.1%
White	30 93.8%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glioblastoma	Anaplastic Glioma
Arm/Group Description	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.	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.
Measure Participants	16	14
Median (95% Confidence Interval) [months]	1.58	2.12

2. Secondary Outcome

Title	Determine Metabolic Effects of Perifosine on Malignant Gliomas by PET Imaging
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Treatment
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Treatment
Arm/Group Description	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.
All Cause Mortality
	Treatment
	Affected / at Risk (%)	# Events
Total	30/32 (93.8%)
Serious Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	22/32 (68.8%)
Eye disorders
Ophthalmoplegia/diplopia (double vision)	1/32 (3.1%)
Gastrointestinal disorders
Diarrhea	1/32 (3.1%)
Hemorrhage, Upper GI NOS	1/32 (3.1%)
Nausea	1/32 (3.1%)
Pain - Stomach	1/32 (3.1%)
General disorders
Death not assoc w CTCAE term- Death NOS	1/32 (3.1%)
Death not assoc w CTCAE term-Disease prog NOS	3/32 (9.4%)
Extremity-lower (gait/walking)	4/32 (12.5%)
Fatigue (asthenia, lethargy, malaise)	1/32 (3.1%)
Fever (in the absence of neutropenia)	1/32 (3.1%)
Pain - Pain NOS	1/32 (3.1%)
Infections and infestations
Inf unknown ANC-Pneumonia(lung)	1/32 (3.1%)
Infection w/ Gr 3/4 neut, Wound	1/32 (3.1%)
Investigations
Platelets	1/32 (3.1%)
Musculoskeletal and connective tissue disorders
Muscle weakness - Extremity-lower	1/32 (3.1%)
Muscle weakness - Left-sided	4/32 (12.5%)
Muscle weakness - Whole body/general	3/32 (9.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malig-poss related to ca txt specify	2/32 (6.3%)
Nervous system disorders
Hemorrhage, CNS	1/32 (3.1%)
Memory impairment	1/32 (3.1%)
Neurology - Other (specify)	3/32 (9.4%)
Nrpthy:cranl-CN X Mtr-palate;phrynx,lrynx	1/32 (3.1%)
Pain - Head/headache	1/32 (3.1%)
Seizure	13/32 (40.6%)
Somnolence/dprssd level of conscious	3/32 (9.4%)
Speech impairment	3/32 (9.4%)
Psychiatric disorders
Confusion	2/32 (6.3%)
Mood alteration - Agitation	1/32 (3.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/32 (3.1%)
Vascular disorders
Thrombosis/thrombus/embolism	2/32 (6.3%)
Other (Not Including Serious) Adverse Events
	Treatment
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Blood and lymphatic system disorders
Neutropenia	1/32 (3.1%)
Gastrointestinal disorders
Diarrhea	7/32 (21.9%)
Nausea	5/32 (15.6%)
Vomiting	2/32 (6.3%)
General disorders
Fatigue	10/32 (31.3%)
Investigations
Lymphopenia	3/32 (9.4%)
Increased alanine aminotransferase	13/32 (40.6%)
Thrombocytopenia	9/32 (28.1%)
Elevated aspartate transaminase (AST)	6/32 (18.8%)
Leukopenia	5/32 (15.6%)
Alkaline phosphatase	3/32 (9.4%)
Metabolism and nutrition disorders
Hyperglycemia	16/32 (50%)
Hypophosphatemia	2/32 (6.3%)
Hypophosphatemia	5/32 (15.6%)
Hyperkalemia	2/32 (6.3%)
Hypernatremia	1/32 (3.1%)
Hypertriglyceridemia	1/32 (3.1%)
Nervous system disorders
Dysgeusia	1/32 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.