Clinical Trials /

Pediatric Precision Laboratory Advanced Neuroblastoma Therapy

NCT02559778

Description:

A prospective open label, multicenter study to evaluate the feasibility and acute toxicity of using molecularly guided therapy in combination with standard therapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Pediatric Precision Laboratory Advanced <span class="go-doc-concept go-doc-disease">Neuroblastoma</span> Therapy

Title

  • Brief Title: Pediatric Precision Laboratory Advanced Neuroblastoma Therapy
  • Official Title: PEDS-PLAN - Pediatric Precision Laboratory Advanced Neuroblastoma Therapy- A Pilot Study Using Molecular Guided Therapy With Induction Chemotherapy Followed by Maintenance With DFMO for Subjects With Newly Diagnosed High-Risk Neuroblastoma
  • Clinical Trial IDs

    NCT ID: NCT02559778

    ORG ID: NMTRC012

    Trial Conditions

    Neuroblastoma

    Trial Interventions

    Drug Synonyms Arms
    bortezomib Velcade Addition of Targeted Agent
    crizotinib XALKORI Addition of Targeted Agent
    dasatinib Sprycel Addition of Targeted Agent
    lapatinib Tykerb Addition of Targeted Agent
    sorafenib Nexavar Addition of Targeted Agent
    vorinostat ZOLINZA Addition of Targeted Agent
    DFMO Eflornithine, -difluoromethylornithine Addition of Targeted Agent

    Trial Purpose

    A prospective open label, multicenter study to evaluate the feasibility and acute toxicity
    of using molecularly guided therapy in combination with standard therapy followed by
    maintenance therapy with DFMO in subjects with newly diagnosed high risk neuroblastoma.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Addition of Targeted Agent Experimental The addition of one targeted therapy (bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat), determined using genomic profiling of tumor will be combined with standard upfront treatment during cycles 3-6 of induction chemotherapy. This will be followed by consolidation, immunotherapy and then 2 years of DFMO as maintenance. bortezomib, crizotinib, dasatinib, lapatinib, sorafenib, vorinostat, DFMO

    Eligibility Criteria

    Inclusion Criteria:

    - Diagnosis: Subjects must have a diagnosis of high-risk (defined in protocol)
    neuroblastoma or ganglioneuroblastoma (nodular or intermixed) verified by histology
    or demonstration of clumps of tumor cells in bone marrow with elevated urinary
    catecholamine metabolites.

    - Subjects must be age 21 years at initial diagnosis

    - Subjects must not have had prior systemic therapy except for localized emergency
    radiation to sites of life-threatening or function-threatening disease and/or no more
    than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as
    per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification
    status and histology.

    - Specimens will be obtained only in a non-significant risk manner and not solely for
    the purpose of investigational testing.

    - Adequate liver function must be demonstrated (defined in protocol)

    - Subjects must have adequate renal function defined as a Serum creatinine based on
    age/gender (defined in protocol)

    - Adequate Cardiac Function (defined in protocol)

    - Ability to tolerate PBSC collection: No known contraindication to PBSC collection.

    - A negative serum pregnancy test is required for female participants of child bearing
    potential (13 years of age or after onset of menses)

    - 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 six months 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:

    - Subjects who are 12-18 months of age with INSS Stage 4 and all stage 3 subjects with
    favorable biologic features (ie, nonamplified MYCN, favorable pathology, and DNA
    index > 1) are not eligible.

    - Lactating females are not eligible unless they have agreed not to breastfeed their
    infants.

    - Subjects receiving any investigational drug concurrently.

    - Subjects with any other medical condition, including but not limited to malabsorption
    syndromes, mental illness or substance abuse, deemed by the Investigator to be likely
    to interfere with the interpretation of the results or which would interfere with a
    subject's ability to sign or the legal guardian's ability to sign the informed
    consent, and subject's ability to cooperate and participate in the study

    Minimum Eligible Age: 12 Months

    Maximum Eligible Age: 21 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Number of subjects that have a targeted agent chosen for treatment.

    Number of subjects that receive 75% of dosing of medications while on study protocol during cycles 3-6.

    Number of subjects required to go off therapy due to treatment-related adverse events as assessed by CTCAE v4.0.

    Number of subjects that are able to complete 2 years of DFMO therapy.

    Secondary Outcome Measures

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Overall Response Rate (ORR) of Participants by the presence of radiologically assessable disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans.

    Number of days that subjects remain disease free

    Trial Keywords