A Phase I Trial and Pharmacokinetic Study of the Oral Platinum Analog Satraplatin in Children and Young Adults With Refractory Solid Tumors Including Brain Tumors
The platinum compounds cisplatin and carboplatin are standard agents in the treatment of a
variety of childhood cancers. However, cumulative and long-term renal and ototoxicity are a
concern related to cisplatin administration, particularly in young children.
Several mechanisms of resistance to platinum compounds have been described including
decreased drug accumulation due to altered drug uptake or the presence of a membrane efflux
pump, increased intracellular levels of thiol-containing groups that detoxify and modulate
platinum, and removal of the platinum-DNA adducts by DNA repair pathways called nucleotide
excision repair (NER) and base excision repair (BER) pathways.
Polymorphisms in DNA repair genes have been shown in some cancers to predict better
treatment response to platinum treatment.
Satraplatin is an oral platinum analog with similar preclinical in vitro and in vivo
activity to that of cisplatin and carboplatin, and with activity in platinum resistant
Dose-limiting satraplatin toxicities in adults include nausea, vomiting, and
myelosuppression. Neither renal nor neurologic toxicities have been described.
Satraplatin has demonstrated clinical activity in adult refractory tumors at the recommended
phase II and III dose of 80 mg/m2/dose daily for 5 days every 28 or 35 days.
To determine the maximum tolerated dose (MTD) of oral satraplatin administered on a once
daily for 5 days every 28 days schedule in pediatric patients with relapsed or refractory
solid tumors including brain tumors.
To define the toxicities of oral satraplatin and characterize the pharmacokinetics of oral
satraplatin in children with refractory cancer.
To determine the preliminary antitumor activity of satraplatin.
To evaluate the pharmacogenomic expression of DNA repair genes in peripheral blood
mononuclear blood cells.
Patients greater than or equal to 3 years and less than or equal to 25 years at enrollment
with relapsed or refractory solid tumors including brain tumors.
Adequate organ function
This is a phase I trial of satraplatin administered once daily orally for 5 days every 28
days. A cycle of therapy is considered to be 28 days. The starting dose level is 60
mg/m(2)/dose with escalations to 80, 110, 140 mg/m(2)/dose. The MTD will be defined based on
satraplatin tolerability during cycle one.
Disease status will be evaluated prior to every odd treatment cycle and therapy may continue
for up to 2 years in the absence of progressive disease or unacceptable toxicity.
Plasma pharmacokinetics and pharmacogenomics will be evaluated during the first treatment
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the maximum tolerated dose (MTD) of oral satraplatin administered on a once daily for 5 days every 28 days schedule in pediatric patients with relapsed or refractory solid tumors including brain tumors.
Brigitte C Widemann, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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