Trial of Tolcapone With Oxaliplatin for Neuroblastoma

NCT ID: NCT02630043

Last Updated: 2024-08-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2019-07-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tolcapone

Intervention Type: 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.

Oxaliplatin

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Oxaliplatin

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

Intervention Type: DRUG

Other Intervention Names

Tasmar; Eloxatin

Eligibility 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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Giselle Sholler

OTHER

Sponsor Role: lead

Responsible Party

Giselle Sholler

Study Chair

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jessica Foley, MD

Role: STUDY_CHAIR

Spectrum Health Hospitals

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Rady Children's Hospital

San Diego, California, United States

Connecticut Children's Hospital

Hartford, Connecticut, United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Levine Children's Hospital

Charlotte, North Carolina, United States

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

Hershey, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

http://www.beatcc.org

Consortium website

Other Identifiers

NMTRC011

Identifier Type: -

Identifier Source: org_study_id