NeuroblastomaPhase 1NCT02630043
Trial of Tolcapone With Oxaliplatin for Neuroblastoma
A Phase 1 study testing Tolcapone and Oxaliplatin in people with Neuroblastoma, run by Giselle Sholler at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Tolcapone and Oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 9 sitesUnited States
- Study dates
- Dec 2015to Jul 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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:
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
Levine Children's Hospital
Charlotte, North Carolina, 28204
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, 17033
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96813
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Rady Children's Hospital
San Diego, California, 92123
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
About this study
Official title: A Phase I Trial of Tolcapone Alone and in Combination With Oxaliplatin in Patients With Relapsed or Refractory Neuroblastoma
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
- Being tested
- Tolcapone, Oxaliplatin
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolcaponeDrug
Also called Tasmar
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.
OxaliplatinDrug
Also called Eloxatin
Oxaliplatin will be given starting in Cycle 2 at 100 mg/m2 IV on Day 1 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tolcapone; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (7)
Determine the Overall Response Rate (ORR) of Participants using RECIST criteria
To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG or PET scans.
Measured: 3 years
Determine the Progression Free Survival (PFS) of Participants using days until progression
To evaluate the activity of tolcapone in combination with oxaliplatin in relapsed or refractory neuroblastoma based on:
Progression free survival (PFS)
Measured: 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).
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Measured: 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).
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Measured: 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.
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Measured: 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 Peak Plasma Concentration (Cmax)
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Measured: 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 Area Under the Curve (AUC).
Tolcapone plasma concentration-time data will be determined for all subjects enrolled on study.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionJul 2019
- Study completionJul 2019
Why it stopped: Lack of study enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Giselle Sholler
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Giselle Sholler, Milton S. Hershey Medical Center
- Investigators
- Jessica Foley, MD, Study chair, Corewell Health West
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630043
- Sponsor's protocol ID
- NMTRC011
- Status last verified
- Aug 2024
- First submitted
- 4 Dec 2015
- Last updated
- 6 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Tolcapone Alone and in Combination With Oxaliplatin in Patients With Relapsed or Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT02630043
- Acronym / sponsor ID
- NMTRC011
- Conditions
- Neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of study enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Giselle ShollerUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Jul 2019 (actual)
- Study completion
- Jul 2019 (actual)
- First posted
- 15 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tolcapone and Oxaliplatin | Experimental | Drug: Tolcapone, Drug: OxaliplatinSubjects 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. |
Who may qualify
- Ages
- 0 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- 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:
- 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
Key exclusion criteria (17 listed)
- 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:
- Investigational Drugs: Subjects who have received another investigational drug within the last 14 days are excluded from participation.
- Subjects with CNS lesions are excluded
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolcaponeAlso: TasmarTolcapone 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. | Drug | Tolcapone and Oxaliplatin |
| OxaliplatinAlso: EloxatinOxaliplatin will be given starting in Cycle 2 at 100 mg/m2 IV on Day 1 of each 21-day cycle | Drug | Tolcapone and Oxaliplatin |
Primary outcome
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
7 secondary outcomes
Determine the Overall Response Rate (ORR) of Participants using RECIST criteria
Time frame: 3 years
Determine the Progression Free Survival (PFS) of Participants using days until progression
Time frame: 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).
Time frame: 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).
Time frame: 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.
Time frame: 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 Peak Plasma Concentration (Cmax)
Time frame: 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 Area Under the Curve (AUC).
Time frame: 24 hours
Results and safety
The study was stopped early (reason given: Lack of study enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Consortium websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica Foley, MD study chair
Corewell Health West
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tolcapone and Oxaliplatin in people with Neuroblastoma, run by Giselle Sholler at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of study enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.