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Trial record 5 of 7 for:    DFMO and neuroblastoma

Study of DFMO in Combination With Bortezomib for Relapsed or Refractory Neuroblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Spectrum Health Hospitals
Sponsor:
Collaborators:
Beat NB Cancer Foundation
Because of Ezra
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT02139397
First received: May 13, 2014
Last updated: April 25, 2017
Last verified: April 2017
  Purpose
The purpose of this research study is to evaluate an investigational drug (DFMO) in combination with bortezomib, for relapsed and refractory neuroblastoma. DFMO is an investigational drug because it has not been approved by the U.S. Food and Drug Administration (FDA). This study will look at the safety and tolerability of DFMO in combination with bortezomib as well as the tumors response to this study drug.

Condition Intervention Phase
Neuroblastoma Recurrent
Drug: DFMO
Drug: Bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of DFMO in Combination With Bortezomib in Patients With Relapsed or Refractory Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Spectrum Health Hospitals:

Primary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ]
    Phase I- To determine the safety and tolerability of DFMO in combination with bortezomib at 3 dose levels of DFMO: 1500mg/m2 twice daily, 2000mg/m2 twice daily, and 2500mg/m2 twice daily in subjects with relapsed or refractory neuroblastoma who receive one full cycle of this dose.

  • Determine the Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 3 years ]
    To determine the overall response rate (ORR) by the presence of radiologically assessable disease by cross-sectional imaging and in MIBG or PET scans.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ]
    Phase II- To continue to determine the safety and tolerability of DFMO in combination with bortezomib in subjects with relapsed or refractory neuroblastoma.

  • Determine the Progression Free Survival (PFS) of Participants using days until progression [ Time Frame: 3 years ]

    To evaluate the activity of DFMO in combination with bortezomib based on:

    - Progression free survival (PFS)


  • Correlate PET scan changes with Progression Free Survival [ Time Frame: 3 years ]
    For subjects followed with PET scan: comparison of changes in PET activity and correlation with PFS

  • Biology studies [ Time Frame: 3 years ]
    Urine, blood, bone marrow and tumor biological Correlates will be explored. Dose effect of DFMO on biological correlates will also be explored.

  • Correlate urinary polyamine levels with response and progression of disease in neuroblastoma. [ Time Frame: 3 years ]
    Correlation of urinary polyamine levels with response and progression of disease in neuroblastoma.


Estimated Enrollment: 38
Actual Study Start Date: May 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DFMO and Bortezomib
Subjects will take DFMO by mouth 2 times a day for each day of a 21 day cycle and Bortezomib will be given by IV push on days 1, 4, and 8 of each 21 day cycle.
Drug: DFMO
Other Names:
  • D,L-ɑdifluoromethylornithine
  • Eflornithine
Drug: Bortezomib
Other Name: Velcade

  Eligibility

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

Inclusion Criteria:

  • Age: ≤ 21 years at the time of diagnosis.
  • Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
  • Disease Status: For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound. Patients must have ONE of the following:
  • First episode of recurrent disease following completion of aggressive multi-drug frontline therapy.
  • First 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 protocol (examples include Children's Oncology Group trials: A3973, ANBL0532, ANBL09P1, etc.).
  • Measurable or evaluable disease, including at least one of the following: Measureable tumor by CT or MRI; or A positive MIBG or PET scan; or Positive bone marrow biopsy/aspirate.
  • Current disease state must be one for which there is currently no known curative therapy or no additional therapies proven to prolong survival with an acceptable quality of life.
  • A negative urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
  • Organ Function Requirements:

    1. Subjects must have adequate liver function as defined by:

      • AST and ALT <5x upper limit of normal
      • Serum bilirubin must be ≤ 2.0 mg/dl
    2. Subjects must have adequate Bone Marrow function defined as:

For patients without bone marrow involvement:

  • Peripheral absolute neutrophil count (ANC) ≤ 750/uL
  • Platelet count 50,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment. Exception: Patients that are platelet dependent due to previous extensive treatment- e.g. - MIBG therapy).
  • Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions) Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and platelet count criteria are met but are not evaluable for hematological toxicity.

    • Subjects must have adequate renal function defined as: Serum creatinine based on age/gender.
    • 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 <0.25
  • Prior Therapy- Patients must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:

    1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
    2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
    3. 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.
    4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines.
    5. Monoclonal antibodies: At least 7 days or 3 half-lives, whichever is longer, must have elapsed since prior treatment with a monoclonal antibody.
    6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
    7. 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.
  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02139397

Contacts
Contact: Genevieve Bergendahl, RN 616-267-0335 genevieve.bergendahl@helendevoschildrens.org

Locations
United States, Arkansas
Arkansas Children's Hospital Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Janet Storment, RN    501-364-2760    StormentJanetS@uams.edu   
Principal Investigator: Kathleen Neville, MD         
United States, Connecticut
Connecticut Children's Hospital Recruiting
Hartford, Connecticut, United States, 06106
Contact: Sharon Huie-White    860-545-9337    shuie@connecticutchildrens.org   
Principal Investigator: Michael Isakoff, MD         
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson Recruiting
Orlando, Florida, United States, 32806
Contact: Michelle Pope, RN    321-841-8588      
Principal Investigator: Don Eslin, MD         
United States, Michigan
Helen DeVos Children's Hospital Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Shannon MacKeigan    616-267-1162    shannon.mackeigan@helendevoschildrens.org   
Principal Investigator: Deanna Mitchell, MD         
Principal Investigator: Giselle Sholler, MD         
United States, Missouri
Children's Mercy Hospitals and Clinics Recruiting
Kansas City, Missouri, United States, 64108
Contact: Michelle Dinkins    816-302-6893    MDinkins@cmh.edu   
Principal Investigator: Keith August, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Liz Shewfelt    843-792-2957    shewfelt@musc.edu   
Principal Investigator: Jaqueline Kraveka, MD         
Sponsors and Collaborators
Giselle Sholler
Beat NB Cancer Foundation
Because of Ezra
Investigators
Study Chair: Kathleen Neville, MD Children's Mercy Hospital
  More Information

Additional Information:
Responsible Party: Giselle Sholler, NMTRC Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT02139397     History of Changes
Other Study ID Numbers: NMTRC010
Study First Received: May 13, 2014
Last Updated: April 25, 2017

Additional relevant MeSH terms:
Neuroblastoma
Eflornithine
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
Bortezomib
Antineoplastic Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Ornithine Decarboxylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 28, 2017