ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02630043
Previous Study | Return to List | Next Study

Trial of Tolcapone With Oxaliplatin for Neuroblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02630043
Recruitment Status : Recruiting
First Posted : December 15, 2015
Last Update Posted : April 19, 2018
Sponsor:
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals

Brief Summary:
The purpose of this research study is to evaluate an investigational drug (Tolcapone) alone and in combination with oxaliplatin, for relapsed and refractory neuroblastoma. Tolcapone is approved by the U.S. Food and Drug Administration (FDA) for adults, but is an investigational drug in this study because it has not been approved in pediatrics for this indication. Oxaliplatin, although a drug approved by the FDA for other cancers, is investigational for treatment of neuroblastoma in this study. This study will look at the safety and tolerability of tolcapone in combination with oxaliplatin as well as the tumors response to this study drug.

Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: Tolcapone Drug: Oxaliplatin Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Tolcapone Alone and in Combination With Oxaliplatin in Patients With Relapsed or Refractory Neuroblastoma
Study Start Date : December 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: Tolcapone and Oxaliplatin

Subjects will receive oral tolcapone at their assigned dose level on each day of this 21-day cycle.

Oxaliplatin will be given at 100 mg/m2 IV on Day 1 of Cycle 2 through 5 and any subsequent 21-day cycle.

Drug: Tolcapone
Tolcapone is an oral agent that will be administered every day of each 21-day cycle during Cycle 1 and in combination with oxaliplatin during cycles 2-5 given IV on Day 1 of each 21-day cycle.
Other Name: Tasmar

Drug: Oxaliplatin
Oxaliplatin will be given starting in Cycle 2 at 100 mg/m2 IV on Day 1 of each 21-day cycle
Other Name: Eloxatin




Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]
    To determine the safety and tolerability of tolcapone alone and in combination with oxaliplatin at 4 dose levels of tolcapone


Secondary Outcome Measures :
  1. Determine the Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 3 years ]
    To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG or PET scans.

  2. Determine the Progression Free Survival (PFS) of Participants using days until progression [ Time Frame: 3 years ]

    To evaluate the activity of tolcapone in combination with oxaliplatin in relapsed or refractory neuroblastoma based on:

    Progression free survival (PFS)


  3. To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Plasma half-life (t1/2). [ Time Frame: 24 hours ]
    Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.

  4. To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Plasma clearance (Cl). [ Time Frame: 24 hours ]
    Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.

  5. To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Vd. [ Time Frame: 24 hours ]
    Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.

  6. To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Peak Plasma Concentration (Cmax) [ Time Frame: 24 hours ]
    Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.

  7. To evaluate the drug levels and pharmacokinetics (PK) of Tolcapone from blood samples at multiple time points within the first 24 hours on study based on Area Under the Curve (AUC). [ Time Frame: 24 hours ]
    Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: ≤ 21 years at the time of study entry.
  2. Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
  3. Disease Status: Patients must have ONE of the following:

    • Any episode of recurrent disease following completion of aggressive multi-drug frontline therapy.
    • Any episode of progressive disease during aggressive multi-drug frontline therapy.
    • Primary resistant/refractory disease detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocols.
  4. Measurable or evaluable disease, including at least one of the following: measureable tumor by CT or MRI; a positive MIBG, or PET scan; positive bone marrow biopsy/aspirate.
  5. Current disease state must be one for which there is currently no known curative therapy
  6. A negative urine or serum pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
  7. Organ Function Requirements:

    • Subjects must have adequate liver function as defined by:

      • AST and ALT ≤ upper limit of normal
      • Serum bilirubin must be ≤ 2.0 mg/dl
    • Subjects must have adequate Bone Marrow function defined as:

For patients without bone marrow involvement:

• Peripheral absolute neutrophil count (ANC) >750/uL

  • Subjects must have adequate renal function
  • Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for 90 days after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
  • Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines.

Exclusion Criteria:

  • Lansky score <50%
  • BSA (m2) of <0.5
  • Prior Therapy- Patients must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:

    • Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
    • Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
    • Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
    • Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
    • Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody.
    • XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
    • Stem Cell Transplant or Rescue: No evidence of active graft vs. host disease and ≥ 2 months must have elapsed since transplant.
  • Investigational Drugs: Subjects who have received another investigational drug within the last 14 days are excluded from participation.
  • Subjects with CNS lesions are excluded
  • Subjects with a history of depression, anxiety, or psychotic disorders (due to tolcapone adverse event profile).
  • Subjects that are pregnant or breastfeeding an infant.
  • Subjects that cannot swallow tablets.
  • Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
  • Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02630043


Contacts
Contact: Genevieve Bergendahl, MSN 6162670335 genevieve.bergendahl@helendevoschildrens.org
Contact: Alyssa VanderWerff 6162670327 alyssa.vanderwerff@helendevoschildrens.org

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Janet Storment, RN    501-364-2760    StormentJanetS@uams.edu   
Principal Investigator: Kathleen Neville, MD         
United States, California
Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Mehrzad Milburn    858-966-8155      
Principal Investigator: William Roberts, MD         
United States, Connecticut
Connecticut Children's Hospital Not yet recruiting
Hartford, Connecticut, United States, 06106
Contact: Sharon Huie-White    860-545-9337    shuie@connecticutchildrens.org   
Principal Investigator: Michael Isakoff, MD         
United States, Hawaii
Kapiolani Medical Center for Women and Children Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Andrea Siu, MPH    808-535-7169    andrea.siu@kapiolani.org   
Principal Investigator: Randal Wada, MD         
United States, Michigan
Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Shannon MacKeigan, R    616-267-1162    shannon.mackeigan@helendevoschildrens.org   
Principal Investigator: Deanna Mitchell, MD         
Principal Investigator: Giselle Sholler, MD         
United States, Missouri
Cardinal Glennon Children's Medical Center Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Katherine Maxwell, RN    314-268-4000      
Principal Investigator: William Ferguson, MD         
United States, North Carolina
Levine Children's Hospital Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Nicole Turner, RN    980-442-2355    felisha.turner@carolinashealthcare.org   
Principal Investigator: Javier Oesterheld, MD         
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center and Children's Hospital Not yet recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Suzanne Treadway       streadway@hmc.psu.edu   
Principal Investigator: Valerie Brown, MD         
United States, South Carolina
Medical University of South Carolina Not yet recruiting
Charleston, South Carolina, United States, 29425
Contact: Liz Shewfelt    843-792-2957    shewfelt@musc.edu   
Principal Investigator: Jaqueline Kraveka, MD         
Sponsors and Collaborators
Giselle Sholler
Investigators
Study Chair: Jessica Foley, MD Spectrum Health Hospitals

Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT02630043     History of Changes
Other Study ID Numbers: NMTRC011
First Posted: December 15, 2015    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Oxaliplatin
Tolcapone
Antineoplastic Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Catechol O-Methyltransferase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action