Trial of Tolcapone With Oxaliplatin for Neuroblastoma

NCT02630043 | Terminated Phase 1 DMC

• 1 other identifier: NMTRC011
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 9

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.

Conditions

Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  To determine the safety and tolerability of tolcapone alone and in combination with oxaliplatin at 4 dose levels of tolcapone

  2 years

Secondary Outcomes (7)

• Determine the Overall Response Rate (ORR) of Participants using RECIST criteria

  3 years

• Determine the Progression Free Survival (PFS) of Participants using days until progression

  3 years

• 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).

  24 hours

• 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).

  24 hours

• 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.

  24 hours

Study Arms (1)

Tolcapone and Oxaliplatin

EXPERIMENTAL

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; Drug: Oxaliplatin

Interventions

Tolcapone DRUG

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.

Also known as: Tasmar

Tolcapone and Oxaliplatin

Oxaliplatin DRUG

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

Also known as: Eloxatin

Tolcapone and Oxaliplatin

Eligibility Criteria

• Age: 0 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: ≤ 21 years at the time of study entry.
• Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
• 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.
• 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.
• Current disease state must be one for which there is currently no known curative therapy
• A negative urine or serum pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Giselle Sholler: lead

Study Sites (9)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96813, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

Penn State Milton S. Hershey Medical Center and Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Links

• Consortium website

MeSH Terms

Conditions

Neuroblastoma

Interventions

Tolcapone; Oxaliplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitrophenols; Phenols; Ketones; Nitro Compounds; Coordination Complexes

Study Officials

• Jessica Foley, MD

  Corewell Health West

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Chair

Study Record Dates

• First Submitted: December 4, 2015
• First Posted: December 15, 2015
• Study Start: December 1, 2015
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: August 6, 2024

Record last verified: 2024-08

Locations

US (9)