Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00776867

Collaborator

University of Wisconsin, Madison (Other), Duke University (Other), AEterna Zentaris (Industry)

Enrollment

Location

Arm

105

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: perifosine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

38 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2008

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Jul 1, 2017

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of perifosine monotherapy in children with cancer [conclusion of the study]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.