Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors

Phase I Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors

The purpose of this study is to test whether perifosine- a drug that inhibits the protein AKT, and has had some success in the treatment of adult cancers- is safe and effective in treating cancer. The investigators want to find out what effects, good and/or bad, it has on the patient and the cancer. The investigators are testing different dose schedules of perifosine and the patient will be asked to partake in one of the dose schedules.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: perifosine

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any solid tumor that failed standard therapy.
• Patient must have evidence for tumor by CT, MRI, PET scan, MIBG scan, serum markers, or tissue sampling.
• Age ≤ 21 years.
• 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 ≥ 75k at least one week off platelet transfusions
• Hg≥ 8g/dL at least one week off PRBC transfusion
• AST ≤ 3 x the upper limit of normal
• ALT ≤ 3 x the upper limit of normal
• Total bilirubin ≤ 2.0 mg/dl
• 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 B-HCG pregnancy test documented within 14 days prior to drug initiation. Females must not be breast feeding.
• Patients must be able to swallow tablets whole

Exclusion Criteria:

• Pregnancy
• 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. HIV testing not required.
• Patients must not be taking EIAEDs. If patients were previously EIAEDs that have been discontinued, patients must have been off the agent for at least 2 weeks prior to registration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: perifosine; This will be a dose escalation study to determine the maximum tolerated dose (MTD) of perifosine alone in recurrent/progressive pediatric tumors. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level.

Drug: perifosine; Open label, phase I study of oral perifosine in recurrent/progressive pediatric solid tumors. This will be a dose escalation study to determine the maximum tolerated dose (MTD) of perifosine alone in recurrent/progressive pediatric tumors. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level. All patients will receive perifosine at a loading dose on the first day, followed by a maintenance dose to start on day two until progression each patient will be assigned to a dosing group based on one's body surface area (BSA).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD) of perifosine monotherapy in children with cancer	conclusion of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine whether pharmacokinetic serum levels correlate with toxicity	conclusion of the study
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	conclusion of the study

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: University of Wisconsin, Madison; Duke University; AEterna Zentaris

Publications and helpful links

General Publications

• Kushner BH, Cheung NV, Modak S, Becher OJ, Basu EM, Roberts SS, Kramer K, Dunkel IJ. A phase I/Ib trial targeting the Pi3k/Akt pathway using perifosine: Long-term progression-free survival of patients with resistant neuroblastoma. Int J Cancer. 2017 Jan 15;140(2):480-484. doi: 10.1002/ijc.30440. Epub 2016 Sep 30.
• Sun W, Modak S. Emerging treatment options for the treatment of neuroblastoma: potential role of perifosine. Onco Targets Ther. 2012;5:21-9. doi: 10.2147/OTT.S14578. Epub 2012 Mar 2.

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2017

Study Registration Dates

• First Submitted: October 20, 2008
• First Submitted That Met QC Criteria: October 20, 2008
• First Posted (Estimate): October 21, 2008

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Pediatric; solid tumors; Pediatric solid tumors; 08-091
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 08-091