Phase I Study of Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- perifosine + temsirolimus
- Conditions
- Pediatric Solid Tumors
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of perifosine + temsirolimus combination in children with cancer.
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
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.
Arms & Interventions
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.
Intervention: perifosine + temsirolimus
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of perifosine + temsirolimus combination in children with cancer.
Time Frame: 2 years
Secondary Outcomes
- 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)