Clinical trial NCT01049841: Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors
Official title: Phase I Study of Perifosine With Temsirolimus for Recurrent Pediatric Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pediatric Solid Tumors
Keywords: pediatric
children
perifosine
temsirolimus
recurrent
progressive
09-124
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: University of Wisconsin, Madison
name: Duke University
name: NATL COMP CA NETWORK
name: Pfizer
name: AEterna Zentaris
First posted: 2010-01-15
Enrollment: 23
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
* 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of perifosine + temsirolimus combination in children with cancer.
timeFrame: 2 years
Secondary outcomes:
measure: To determine whether pharmacokinetic serum levels of both perifosine and temsirolimus correlate with toxicity.
timeFrame: 2 years
measure: To record preliminary data on the efficacy of the perifosine + temsirolimus combination.
timeFrame: 2 years
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ira Dunkel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.