Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier:
NCT01059071
First received: January 26, 2010
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

The purpose of this research study is to evaluate a new investigational drug to treat neuroblastoma. This study drug is called DFMO. The objectives of this study will be to monitor for safety and to find a maximum tolerated dose in this population. A secondary objective will be to look at efficacy of DFMO.

The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO and/or etoposide may continue on treatment with the expectation that there will be an overall clinical benefit.

The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), MIBG scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO, and later combined with an already approved drug, etoposide.

The proposed dosing regimen is an oral dose of DFMO two times a day for each day while on study. There will be 5 cycles. Each cycle will be 21 days in length. The first cycle will be DFMO alone. In the second cycle etoposide will be added in and will be given orally once a day for the first 14 days of each cycle (cycles 2-5).


Condition Intervention Phase
Neuroblastoma
Drug: DFMO
Drug: Etoposide
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide

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: length of study plus 30 days ] [ Designated as safety issue: Yes ]
    To determine the safety, tolerability and maximum tolerated dose (MTD) of DFMO as a single agent and in combination with etoposide in pediatric and young adult patients with refractory or recurrent neuroblastoma


Secondary Outcome Measures:
  • To evaluate the activity of DFMO as a single agent and in combination with etoposide in these tumor types based on: Progression free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Determine the Overall Response Rate (ORR) of Participants using RECIST criteria Determine the Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To evaluate the pharmacokinetics (PK) of DFMO as single agent [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Biology studies to include: effect on polyamine depletion, ODC activity, genomic analysis of cells pre- and post- treatment, correlation of in vitro response to in vivo response, flow cytometry of tumor burden in bone marrow and biomarker development [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: February 2010
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: DFMO

    Escalating doses of DFMO in a 3 +3 cohort design.

    DFMO at current cohort Dose Level orally each day for 21 day cycles

    Dose level 1: 500 mg/m2 PO BID Dose level 2: 750 mg/m2 PO BID Dose level 3:1000 mg/m2 PO BID Dose level 4:1500 mg/m2 PO BID

    Other Name: Difluoromethylornithine
    Drug: Etoposide
    Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.
    Other Names:
    • Eposin
    • Etopophos
    • Vepesid
    • VP-16
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 0-21 years at the time of diagnosis.
  • Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
  • Disease Status: Refractory or relapsed neuroblastoma
  • Measurable disease, including at least one of the following:

Measurable tumor >10mm by CT or MRI A positive MIBG and abnormal urinary catecholamine levels Positive bone marrow biopsy/aspirate.

  • Current disease state must be one for which there is currently no known curative therapy.
  • A negative urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
  • Patients without bone marrow metastases must have an ANC > 500/μl and platelet count >50,000/μl
  • Organ Function Requirements Subjects must have adequate liver function as defined by AST or ALT <10x normal Serum bilirubin must be ≤ 2.0 mg/dl Serum creatinine must be ≥ 1.5 mg/dl
  • 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:

  • Life expectancy <2 months or Lansky score <30%
  • 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 the effects of prior chemotherapy (hematological and bone marrow suppression effects)
  • 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: NCT01059071

Locations
United States, California
Children's Hospital of Orange County
Orange, California, United States, 92868
United States, Connecticut
Connecticut Children's Hospital
Hartford, Connecticut, United States, 06106
United States, Florida
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, United States, 32806
United States, Michigan
Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, North Carolina
Levine Children's Hospital
Charlotte, North Carolina, United States, 28204
United States, Vermont
UVM/FAHC
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Giselle Sholler
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
Investigators
Study Chair: Giselle Sholler, MD The Spectrum Health Group
  More Information

Additional Information:
No publications provided

Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT01059071     History of Changes
Other Study ID Numbers: NMTRC 002
Study First Received: January 26, 2010
Last Updated: September 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Health Hospitals:
Refractory Neuroblastoma
Relapsed neuroblastoma

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
Etoposide phosphate
Eflornithine
Etoposide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on August 01, 2014