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Pediatric Precision Laboratory Advanced Neuroblastoma Therapy (PEDS-PLAN)

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ClinicalTrials.gov Identifier: NCT02559778
Recruitment Status : Recruiting
First Posted : September 24, 2015
Last Update Posted : February 15, 2018
Sponsor:
Collaborators:
Dell, Inc.
Beat NB Cancer Foundation
Because of Ezra
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: bortezomib Drug: crizotinib Drug: dasatinib Drug: lapatinib Drug: sorafenib Drug: vorinostat Drug: DFMO Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study Using Molecular Guided Therapy With Induction Chemotherapy 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.
Study Start Date : September 2015
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Active Comparator: Standard Immunotherapy without DFMO
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given BID for 730 days.
Drug: bortezomib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Velcade

Drug: crizotinib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: XALKORI

Drug: dasatinib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Sprycel

Drug: lapatinib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Tykerb

Drug: sorafenib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Nexavar

Drug: vorinostat
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: ZOLINZA

Active Comparator: Standard Immunotherapy with DFMO
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, DFMO will continue to be given BID for 730 days.
Drug: bortezomib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Velcade

Drug: crizotinib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: XALKORI

Drug: dasatinib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Sprycel

Drug: lapatinib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Tykerb

Drug: sorafenib
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: Nexavar

Drug: vorinostat
One of the following drugs will be chosen for each subject based on molecular guided results: bortezomib, crizotinib, dasatinib, lapatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy, and then DFMO for 2 years as maintenance.
Other Name: ZOLINZA

Drug: DFMO
DFMO will be given for 2 years as maintenance to all subjects completing immunotherapy.
Other Name: Eflornithine, α-difluoromethylornithine




Primary Outcome Measures :
  1. Number of subjects that have a targeted agent chosen for treatment. [ Time Frame: 2 years ]

    At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

    1. Subject has a targeted agent identified
    2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
    3. Subject is not removed from study due to targeted agent drug related toxicity.

  2. Number of subjects that receive 75% of dosing of medications while on study protocol during cycles 3-6. [ Time Frame: 2 years ]

    At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

    1. Subject has a targeted agent identified
    2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
    3. Subject is not removed from study due to targeted agent drug related toxicity.

  3. Number of subjects required to go off therapy due to treatment-related adverse events as assessed by CTCAE v4.0. [ Time Frame: 1 year ]

    At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

    1. Subject has a targeted agent identified
    2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
    3. Subject is not removed from study due to targeted agent drug related toxicity.

  4. Number of subjects that are able to complete 2 years of DFMO therapy. [ Time Frame: 3 years ]
  5. 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. [ Time Frame: 3 years plus 5 years follow up ]
    • To measure the response of treatments chosen based on:
    • Overall response rate (ORR) after induction therapy
    • Progression free survival (PFS)

  6. Number of days that subjects remain disease free [ Time Frame: 3 years plus 5 years follow up ]

    To measure the response of treatments chosen based on:

    • Overall response rate (ORR) after induction therapy
    • Progression free survival (PFS)


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis: Subjects must have a diagnosis of 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 with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:

    a) Subjects with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following: i. Age > 18 months (> 547 days) regardless of biologic features or ii. Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or iii. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.

    b) Subjects with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following: i. MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features or ii. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status.

    c) Subjects with newly diagnosed neuroblastoma with INSS Stage 2A/2B with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of age or additional biologic features.

  2. Subjects must be age ≤ 21 years at initial diagnosis
  3. 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.
  4. Specimens will be obtained only in a non-significant risk manner and not solely for the purpose of investigational testing.
  5. Adequate liver function must be demonstrated, defined as:

    1. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age AND
    2. ALT (SGPT) < 10 x upper limit of normal (ULN) for age
  6. Subjects must have adequate renal function defined as a serum creatinine based on age/gender
  7. Adequate Cardiac Function defined as: Shortening fraction of ≥ 27% by echocardiogram, or Ejection fraction of ≥ 50% by radionuclide evaluation or echocardiogram.
  8. Ability to tolerate PBSC collection: No known contraindication to PBSC collection. Examples of contraindications would include a weight or size less than that determined to be feasible at the collecting institution, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure.
  9. A negative serum pregnancy test is required for female participants of child bearing potential (≥13 years of age or after onset of menses)
  10. 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.
  11. 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:

  1. 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.
  2. Lactating females are not eligible unless they have agreed not to breastfeed their infants.
  3. Subjects receiving any investigational drug concurrently.
  4. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02559778


Contacts
Contact: Genevieve Bergendahl, MSN 616-267-0334 genevieve.bergendahl@helendevoschildrens.org
Contact: Alyssa VanderWerff, MS 616-267-0334 alyssa.vanderwerff@helendevoschildrens.org

  Show 23 Study Locations
Sponsors and Collaborators
Giselle Sholler
Dell, Inc.
Beat NB Cancer Foundation
Because of Ezra
Investigators
Study Chair: Giselle Sholler, MD NMTRC

Additional Information:
Responsible Party: Giselle Sholler, NMTRC Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT02559778     History of Changes
Other Study ID Numbers: NMTRC012
First Posted: September 24, 2015    Key Record Dates
Last Update Posted: February 15, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Neuroblastoma
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
Sorafenib
Lapatinib
Vorinostat
Bortezomib
Dasatinib
Eflornithine
Crizotinib
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Histone Deacetylase Inhibitors
Trypanocidal Agents
Antiprotozoal Agents