Clinical Trials /

Neuroblastoma Maintenance Therapy Trial

NCT02679144

Description:

Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 500 to 1000 mg/m2 BID on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neuroblastoma Maintenance Therapy Trial
  • Official Title: NMTT- Neuroblastoma Maintenance Therapy Trial Using Difluoromethylornithine (DFMO)

Clinical Trial IDs

  • ORG STUDY ID: NMTRC014
  • NCT ID: NCT02679144

Conditions

  • Neuroblastoma

Interventions

DrugSynonymsArms
Difluoromethylornithine (DFMO)eflornithineDifluoromethylornithine (DFMO)

Purpose

Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 500 to 1000 mg/m2 BID on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.

Trial Arms

NameTypeDescriptionInterventions
Difluoromethylornithine (DFMO)ExperimentalSubjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 500 to 1000 mg/m2 twice daily on each day of study.
  • Difluoromethylornithine (DFMO)

Eligibility Criteria

        Inclusion Criteria:

          -  All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99
             years of age and classified as high risk at the time of diagnosis. Exception:
             patients who are initially diagnosed as non-high-risk neuroblastoma, but later
             converted (and/or relapsed) to high risk neuroblastoma are also eligible.

          -  All patients must be in complete remission (CR):

               1. No evidence of residual disease on scan

               2. No evidence of disease metastatic to bone marrow.

          -  Specific Criteria by Stratum:

        Stratum 1: All patients must have completed standard upfront therapy that replicates
        treatment which patients who were enrolled on ANBL0032 received, including:

        intensive induction chemotherapy and (if feasible) resection of primary tumor, followed
        by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy,
        followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;.

        All subjects on Stratum 1 must have also met the following criteria:

        • A pre-transplant disease status evaluation that met International Neuroblastoma Response
        Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR
        (partial response) for primary site, soft tissue metastases and bone metastases. Patients
        who meet those criteria must also meet the protocol-specified criteria for bone marrow
        response prior to transplant as outlined below: No more than 10% tumor involvement (based
        on total nucleated cellular content) seen on any specimen from a bilateral bone marrow
        aspirate/biopsy.

        Stratum 2: Neuroblastoma that is in first complete remission following standard upfront
        therapy different from that described for Stratum 1.

        Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction
        chemotherapy and surgical resection of the primary tumor, but that has achieved CR
        following additional therapy.

        Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).

          -  Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of
             mandatory disease staging must be performed:

               -  Tumor imaging studies including

               -  Bilateral bone marrow aspirates and biopsy

               -  This disease assessment is required for eligibility and preferably should be
                  done within 2 weeks prior to enrollment, but must be done within a maximum of 4
                  weeks before enrollment.

          -  Timing from prior therapy:

        Stratum 1: Enrollment no later than 60 days after completion of upfront therapy, (last
        dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance
        therapy.

        Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent
        therapy.

          -  Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and
             patients must have a life expectancy of ≥ 2 months.

          -  All clinical and laboratory studies for organ functions to determine eligibility must
             be performed within 7 days prior to enrollment unless otherwise indicated below.

          -  Patients must have adequate organ functions at the time of registration:

               -  Hematological: Total absolute phagocyte count ≥1000/μL

               -  Liver: Subjects must have adequate liver function

               -  Renal: Adequate renal function

          -  Females of childbearing potential must have a negative pregnancy test. Patients of
             childbearing potential must agree to use an effective birth control method. Female
             patients who are lactating must agree to stop breast-feeding.

          -  Written informed consent in accordance with institutional and FDA (food and drug
             administration) guidelines must be obtained from all subjects (or patients' legal
             representative).

        Exclusion Criteria:

          -  BSA (Body Surface Area) of <0.25 m2.

          -  Investigational Drugs: Subjects who are currently receiving another investigational
             drug are excluded from participation.

          -  Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are
             not eligible. Subjects must have fully recovered from hematological and bone marrow
             suppression effects of prior chemotherapy.

          -  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.
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with event free survival (EFS) during study.
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Length of time that participants experience Overall Survival (OS)
Time Frame:7 years
Safety Issue:
Description:
Measure:Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame:2 years
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax)
Time Frame:1 year
Safety Issue:
Description:Pharmacokinetic assay
Measure:Area under the plasma concentration versus time curve (AUC)
Time Frame:1 year
Safety Issue:
Description:Pharmacokinetic assay
Measure:Time to reach Peak Plasma Concentration (Tmax)
Time Frame:1 year
Safety Issue:
Description:Pharmacokinetic assay
Measure:Number of participants with ODC (Ornithine decarboxylase) single nucleotide polymorphisms.
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Giselle Sholler

Last Updated

September 8, 2016