Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors

Study Overview
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Brief Summary
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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.

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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: perifosine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: perifosine<br>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<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, solid tumors, Pediatric solid tumors, 08-091