Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

March 9, 2017 updated by: Memorial Sloan Kettering Cancer Center

Phase I Study of Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose (MTD) of perifosine + temsirolimus combination in children with cancer.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine whether pharmacokinetic serum levels of both perifosine and temsirolimus correlate with toxicity.
Time Frame: 2 years
2 years
To record preliminary data on the efficacy of the perifosine + temsirolimus combination.
Time Frame: 2 years
2 years
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
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Pfizer
University of Wisconsin, Madison
Duke University
AEterna Zentaris
NATL COMP CA NETWORK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 1, 2010

Primary Completion (ACTUAL)

March 1, 2017

Study Completion (ACTUAL)

March 1, 2017

Study Registration Dates

First Submitted

January 14, 2010

First Submitted That Met QC Criteria

January 14, 2010

First Posted (ESTIMATE)

January 15, 2010

Study Record Updates

Last Update Posted (ACTUAL)

March 10, 2017

Last Update Submitted That Met QC Criteria

March 9, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-124

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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