Clinical trial NCT00776867: Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors
Official title: Phase I Study of Single Agent Perifosine for Recurrent Pediatric Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Pediatric
solid tumors
Pediatric solid tumors
08-091
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: University of Wisconsin, Madison
name: Duke University
name: AEterna Zentaris
First posted: 2008-10-21
Enrollment: 38
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 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of perifosine monotherapy in children with cancer
timeFrame: conclusion of the study
Secondary outcomes:
measure: To determine whether pharmacokinetic serum levels correlate with toxicity
timeFrame: conclusion of the study
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: conclusion of the study
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: Kushner BH, Cheung NV, Modak S, Becher OJ, Basu EM, Roberts SS, Kramer K, Dunkel IJ. A phase I/Ib trial targeting the Pi3k/Akt pathway using perifosine: Long-term progression-free survival of patients with resistant neuroblastoma. Int J Cancer. 2017 Jan 15;140(2):480-484. doi: 10.1002/ijc.30440. Epub 2016 Sep 30.
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.