Satraplatin in Children and Young Adults With Refractory Solid Tumors Including Brain Tumors

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01259479
First received: December 11, 2010
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

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.

Condition Intervention Phase
Solid Tumors
Brain Tumors
Brain Metastases
Drug: Satraplatin
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • MTD [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 9
Study Start Date: December 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Dose escalation, continuous treatment without DLTs
Drug: Satraplatin
Orally, once daily for 5 days repeated every 28 days, dose-escalation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   3 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Age: greater than or equal to 3 years and less than or equal to 25 years of age at the time of study enrollment.
    2. Diagnosis: Patients with refractory solid tumors including brain tumors (including brain metastases). All patients must have had histological verification of the solid tumor at initial diagnosis or relapse with the exception of patients with diffuse intrinsic brainstem tumors, optic pathway tumors, or CNS germ cell tumors with elevations of reliable serum or CSF tumor markers (alpha-fetoprotein or beta-HCG).
    3. Disease status: Patients must have measurable or evaluable disease.
    4. Prior Therapy: Refractory to standard therapy and no other standard curative treatment options are available. Patients must have fully recovered to less than or equal to grade 1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

      i. Stem Cell Transplantation: Patients must be greater than or equal to 3 months since autologous stem cell transplant and greater than or equal to 6 months since allogeneic stem cell transplant prior to study entry.

      ii. Radiation Therapy: Extensive radiation therapy (craniospinal, more than half of the pelvis, TBI) must be completed at least 3 months prior to study entry. The last dose of all other local palliative radiation must be at least 2 weeks prior to study entry.

      iii. Myelosuppressive chemotherapy: The last dose of myelosuppressive chemotherapy must be at least 21 days prior to study entry. Therapy with nitrosoureas must be at least 6 weeks prior to study entry; and therapy with temozolomide must be 4 weeks prior to study entry.

      iv. Investigational anti-cancer agents: The last dose of all investigational agents must be at least 30 days prior to study entry.

      v. Growth factors: The last dose of growth factors such as filgrastim and epoetin must be at least one week prior to study entry. The last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be 2 weeks prior to study entry.

      vi. Biologic anti-cancer agents: The last dose of nonmyelosuppressive biologic agents for the treatment of the patient s cancer must be at least 7 days prior to study entry.

      vii. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.

      viii. Monoclonal antibody: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody. (See table on Children s Oncology Group Phase I Consortium DVL homepage https://members.childrensoncologygroup.org/Disc/devtherapeu tics/default.asp for listing of monoclonal antibody half-lives.)

      ix. Corticosteroids: Patients with brain tumors must be on a stable or tapering dose of corticosteroids for 7 days prior to the date of the baseline scan performed for the purpose of assessing response to therapy on this study.

    5. Performance status: Patients greater than 10 years of age must have a Karnofsky performance level of greater than or equal to 50%, and children less than or equal to 10 years old must have a Lansky performance of greater than or equal to 50% (Appendix I). Patients who are wheelchair bound because of paralysis should be considered ambulatory when they are up in their wheel chair.
    6. Hematologic Function: Patients must have an absolute neutrophil count greater than or equal to 1000/microL, hemoglobin greater than or equal to 9g/dl (transfusion permitted), and platelet greater than or equal to 75,000/?l (transfusion independent).
    7. Hepatic Function: Patients must have bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) for age, with the exception of Gilbert syndrome, and ALT within less than or equal to 3.0 times the ULN.
    8. Renal Function: Patients must have a creatinine clearance or radioisotope GFR greater than or equal to 60ml/min/1.73 m(2) or a normal serum creatinine based on age described below.
  • Less than or equal to 5 years of age: a maximum serum creatinine of 0.8 mg/dL
  • Older than 5 years of age but less than or equal to the age of 10: a maximum serum creatinine of 1.0 mg/dL
  • Older than 10 years of age and less than or equal to the age of 15: a maximum serum creatinine of 1.2 mg/dL
  • Older than 15 years of age: a maximum serum creatinine of 1.5 mg/dL

    9. Informed Consent: Diagnostic or laboratory studies performed exclusively to determine eligibility for this trial must only be done after obtaining written informed consent from all patients or their legal guardians (if the patient is < 18 years old). When appropriate, pediatric patients will be included in all discussions. This can be accomplished through one of the following mechanisms:

    1. the NCI, POB screening protocol,
    2. an IRB-approved institutional screening protocol or
    3. the study-specific protocol.

      Documentation of the informed consent for screening will be maintained in the patient s research chart. Studies or procedures that were performed for clinical indications (not exclusively to determine eligibility) may be used for baseline values even if the studies were done before informed consent was obtained.

      10. Durable Power of Attorney (DPA): All patients > 18 years of age will be offered the opportunity to assign DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.

      EXCLUSION CRITERIA:

      1. Pregnant or breast-feeding females are excluded due to potential risks of fetal and teratogenic adverse events of an investigational agent. Pregnancy tests (urine BhCG) must be obtained prior to enrollment on this study in girls, age 9 years or older. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Abstinence is an acceptable method of birth control.
      2. Last dose of any investigational agent given within the past 30 days. 3. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, or biologic therapy.

      4. Active graft versus host disease.

      5. Graft vs Host Disease (GVHD) therapy or agents to prevent organ rejection post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either GVHD post bone marrow transplant or organ rejection post transplant are not eligible for this trial.

      6. Clinically significant uncontrolled unrelated systemic illness such as serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction.

      7. Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.

      8. Inability to swallow capsules as capsules cannot be crushed or broken

      9. Prior treatment with satraplatin.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01259479

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Brigitte C Widemann, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01259479     History of Changes
Other Study ID Numbers: 110047, 11-C-0047
Study First Received: December 11, 2010
Last Updated: July 24, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Solid Tumors
Maximum Tolerated Dose
Parmacokinetics
Pharmacogenomics
Satraplatin
Cancer
Solid Tumor
Brain Tumor

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasm Metastasis
Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes
Pathologic Processes
Satraplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014