Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborators:	University of Wisconsin, Madison Duke University NATL COMP CA NETWORK Pfizer Keryx / AOI Pharmaceuticals, Inc.
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01049841

Purpose

The purpose of this study is to test the safety and effectiveness of 2 drugs, perifosine in combination with temsirolimus in children with solid tumors. Neither drug is currently part of the standard treatment of solid tumors in children. Both drugs have been tested alone to treat solid tumors in children with little success. There is now new insight that if given together, perifosine and temsirolimus may work together to stop the growth of solid tumors and may also make them shrink. The doctor wants to find out what effects; good and/or bad, perifosine in combination with temsirolimus has on the patient and the cancer. The doctors are testing four different dose schedules of perifosine with temsirolimus and the patient will be asked to partake in one of the dose schedules. The dose schedule will be lower for those enrolled early in the study.

Condition	Intervention	Phase
Pediatric Solid Tumors	Drug: perifosine + temsirolimus	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) of perifosine + temsirolimus combination in children with cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine whether pharmacokinetic serum levels of both perifosine and temsirolimus correlate with toxicity. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To record preliminary data on the efficacy of the perifosine + temsirolimus combination. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
If previously resected tissue is available, determine whether molecular features predict response including, Elevated PI3K/AKT/mTOR signaling, Elevated RAS/MAPK signaling, Cell cycle markers [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	January 2010
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: perifosine + temsirolimus This is a single arm, phase I study. Eligible patients will receive a loading dose of oral perifosine on the first day, followed by a maintenance dose starting on the second day until progression. Each patient is assigned to a group according to their body surface area (BSA). Temsirolimus will be combined with perifosine at four dose levels to determine the MTD for the combination therapy. Temsirolimus dosing will start on the same day as the perifosine load.	Drug: perifosine + temsirolimus The patient will take oral tablets of perifosine at a dose and frequency to be determined their height, weight and time when they enter the study as those entering early will be treated with lower dose levels (dosing frequency will vary from once a week to daily). The patient will receive an intravenous injection of temsirolimus once a week at a dose to be determined by their height, weight and time when they enter the study as those entering early will be treated with lower doses. In addition they will be asked to keep a medicine diary.

Arms

Assigned Interventions

Experimental: perifosine + temsirolimus

This is a single arm, phase I study. Eligible patients will receive a loading dose of oral perifosine on the first day, followed by a maintenance dose starting on the second day until progression. Each patient is assigned to a group according to their body surface area (BSA). Temsirolimus will be combined with perifosine at four dose levels to determine the MTD for the combination therapy. Temsirolimus dosing will start on the same day as the perifosine load.

Drug: perifosine + temsirolimus

The patient will take oral tablets of perifosine at a dose and frequency to be determined their height, weight and time when they enter the study as those entering early will be treated with lower dose levels (dosing frequency will vary from once a week to daily). The patient will receive an intravenous injection of temsirolimus once a week at a dose to be determined by their height, weight and time when they enter the study as those entering early will be treated with lower doses. In addition they will be asked to keep a medicine diary.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Any solid tumor that has failed standard therapy
Patient must have evidence of tumor by CT, MRI, MIBG scan, serum markers, or tissue sampling.
Age ≤ 21 years (age ≤ 35 years for biopsy proven medulloblastoma or neuroblastoma)
Karnofsky/Lansky performance status ≥ 50% (Karnofsky score for age> 16 years and Lansky score for age ≤ 16 years)
ANC≥ 1000 at least 24 hours off GCSF
Platelets ≥ 100K at least one week off platelet transfusions
Hg≥ 8g/dL at least one week off PRBC transfusion
AST ≤ 2 x the upper limit of normal
ALT ≤ 2 x the upper limit of normal
Total bilirubin ≤ 2.0 mg/dl
Patients must have cholesterol level < 350 mg/dl and triglycerides level < 400 mg/dl because temsirolimus can induce hyperlipidemia.
Serum creatinine ≤ 1.5 x the upper limit of normal for age, or calculated creatinine clearance or nuclear GFR ≥ 70 ml/min/1.73 m2.
≥ 3 weeks since last non-nitrourea chemotherapy
≥ 6 weeks since last nitroureas
≥ 4 weeks since last RT
Patients must agree to practice adequate contraception. Females of childbearing potential must have a negative serum B-HCG pregnancy test documented within 14 days prior to registration. Females must not be breast feeding.
Patients must be able to swallow perifosine tablets whole
Patients that participated in the phase I single agent perifosine study for recurrent pediatric solid tumors and did not experience a DLT are eligible to participate in this study and can start ≥ 2 weeks since last dose of perifosine
Patients that have been previously treated with an mTOR inhibitor can still enroll in this trial as long as they did not experience a DLT in the single agent mTOR inhibitor trial

Exclusion Criteria:

Pregnancy
Patients must not have an uncontrolled active infection.
HIV-Positive patients receiving combination anti-retroviral therapy are excluded from the study due to possible retro-viral drug interactions. HIV testing not required.
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.
History of or known pulmonary hypertension or history of or known pneumonitis.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049841

Contacts

Contact: Ira Dunkel, MD	212-639-2153
Contact: Stephen Gilheeney, MD	212-639-3973

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Ira Dunkel, MD 212-639-2153
Contact: Stephen Gilheeney, MD 212-639-3973
Principal Investigator: Ira Dunkel, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

University of Wisconsin, Madison

Duke University

NATL COMP CA NETWORK

Pfizer

Keryx / AOI Pharmaceuticals, Inc.

Investigators

Principal Investigator:

Ira Dunkel, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01049841 History of Changes
Other Study ID Numbers:	09-124
Study First Received:	January 14, 2010
Last Updated:	November 22, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

pediatric
children
perifosine
temsirolimus

recurrent
progressive
09-124

Additional relevant MeSH terms:

Neoplasms
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 23, 2012