Satraplatin in Children and Young Adults With Refractory Solid Tumors Including Brain Tumors
Condition: Solid Tumors; Brain Tumors; Brain Metastases
MeSH terms: Neoplasms; Brain Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  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.

      Objectives:

        -  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.

      Eligibility:

      - 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.

      Design:

        -  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.
    

Detailed description: 
      BACKGROUND

      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.

      OBJECTIVES

      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.

      ELIGIBILITY

      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

      DESIGN

      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.
    

Intervention name(s): Satraplatin
Intervention type(s): Drug
Intervention description(s): Orally, once daily for 5 days repeated every 28 days, dose-escalation
Intervention MeSH terms: Satraplatin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Solid Tumors; Maximum Tolerated Dose; Parmacokinetics; Pharmacogenomics; Satraplatin; Cancer; Solid Tumor; Brain Tumor