Solid Tumors
Conditions
Keywords
Pediatric, solid tumors, Pediatric solid tumors, 08-091
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.
Interventions
DRUGperifosine
Open label, phase I study of oral perifosine in recurrent/progressive pediatric solid tumors. This will be a dose escalation study to determine the maximum tolerated dose (MTD) of perifosine alone in recurrent/progressive pediatric tumors. A standard 3+3 dose escalation design will be employed with 3-6 patients at each dose level. All patients will receive perifosine at a loading dose on the first day, followed by a maintenance dose to start on day two until progression each patient will be assigned to a dosing group based on one's body surface area (BSA).
Sponsors
University of Wisconsin, Madison
Duke University
AEterna Zentaris
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) of perifosine monotherapy in children with cancer | conclusion of the study |
Secondary
| Measure | Time frame |
|---|---|
| To determine whether pharmacokinetic serum levels correlate with toxicity | conclusion of the study |
| 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 | conclusion of the study |
Countries
United States
Outcome results
None listed