Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Wisconsin, Madison
Duke University
NATL COMP CA NETWORK
Pfizer
Aeterna Zentaris GmbH
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01049841
First received: January 14, 2010
Last updated: December 3, 2013
Last verified: December 2013
  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:


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 2015
Estimated Primary Completion Date: January 2015 (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.

  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-nitrosourea chemotherapy
  • ≥ 6 weeks since last nitrosoureas
  • ≥ 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 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
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: NCT01049841

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
University of Wisconsin, Madison
Duke University
NATL COMP CA NETWORK
Pfizer
Aeterna Zentaris GmbH
Investigators
Principal Investigator: Ira Dunkel, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
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: December 3, 2013
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
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014