Perifosine With Temsirolimus 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 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.

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

Conditions
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Pediatric Solid Tumors

Intervention / Treatment
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* Drug: perifosine + temsirolimus


Participation Criteria
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Eligibility Criteria
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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.

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 + temsirolimus<br>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<br>* 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.<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 + temsirolimus combination in children with cancer. |  | 2 years | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, children, perifosine, temsirolimus, recurrent, progressive, 09-124