Satraplatin in Children and Young Adults With Refractory Solid Tumors Including Brain Tumors
- Cisplatin and carboplatin are standard cancer treatment drugs used for various childhood cancers, including brain tumors. Both drugs frequently have severe side effects that may reduce their effectiveness, particularly in children, and new treatments are needed that may be similarly effective but less toxic for cancer patients.
- Satraplatin is an experimental drug, similar to cisplatin and carboplatin, that has not yet been approved by the Food and Drug Administration. Satraplatin has been shown to treat cancer by interfering with genetic material (DNA) in cancer cells. Some adults with cancer who have received satraplatin had slowing of the growth or shrinkage of their tumor. Researchers are interested in determining whether satraplatin can be effective for cancers that occur in children.
- To evaluate the safety and effectiveness of satraplatin as a treatment for children and young adults who have solid tumors that have not responded to standard treatment.
- To study the effects of satraplatin on the body in terms of side effects and blood chemistry.
- To examine the effect that genetic variations may have on the effectiveness of satraplatin.
- Children, adolescents, and young adults between 3 and 21 years of age who have solid tumors (including brain tumors) that have not responded to standard treatment.
- Participants will be screened with a full physical examination and medical history, blood tests, and tumor imaging studies.
- Participants will receive satraplatin pills to be taken every day in the morning for 5 consecutive days, with no food for 2 hours before or 1 hour after the dose. Participants will then have 23 days without the drug to complete a 28-day cycle of treatment. Participants will also receive medication to prevent nausea and vomiting 30 minutes before the first dose of satraplatin. Following the first dose of satraplatin, medication for nausea will be given if needed.
- Satraplatin doses will be adjusted based on response to treatment, including potential side effects. Participants will have frequent blood tests and imaging studies to evaluate the effectiveness of the treatment and monitor any side effects, as well as hearing tests and other examinations as required by the study researchers.
- Participants will receive satraplatin every 4 weeks for up to 2 years until serious side effects occur or the tumor stops responding to treatment.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- MTD [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
- PKs [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
- Definte anti-tumore activity [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
- PGs [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Study Completion Date:||August 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Dose escalation, continuous treatment without DLTs
Orally, once daily for 5 days repeated every 28 days, dose-escalation
Hide Detailed Description
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 models.
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 cycle.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01259479
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Brigitte C Widemann, M.D.||National Cancer Institute (NCI)|