Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors

NCT01049841 | Completed Phase 1

• 1 other identifier: 09-124
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Pediatric Solid Tumors

Keywords

pediatric; children; perifosine; temsirolimus; recurrent; progressive; 09-124

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of perifosine + temsirolimus combination in children with cancer.

  2 years

Secondary Outcomes (3)

• 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

Study Arms (1)

perifosine + temsirolimus

EXPERIMENTAL

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

Interventions

perifosine + temsirolimus DRUG

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.

perifosine + temsirolimus

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• University of Wisconsin, Madison: collaborator
• Duke University: collaborator
• NATL COMP CA NETWORK: collaborator
• Pfizer: collaborator
• AEterna Zentaris: collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 22419878 DERIVED

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Recurrence

Interventions

perifosine; temsirolimus

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ira Dunkel, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 15, 2010
• Study Start: January 1, 2010
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: March 10, 2017

Record last verified: 2017-03

Locations

US (1)