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

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ClinicalTrials.gov Identifier: NCT01059071
Recruitment Status : Completed
First Posted : January 29, 2010
Results First Posted : June 20, 2016
Last Update Posted : October 27, 2016
Information provided by (Responsible Party):

Study Description
Brief Summary:

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 or disease Intervention/treatment Phase
Neuroblastoma Drug: DFMO Drug: Etoposide Phase 1

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
Study Start Date : February 2010
Primary Completion Date : October 2014
Study Completion Date : May 2015

Arms and Interventions

Arm Intervention/treatment
Experimental: DFMO and Etoposide 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

Outcome Measures

Primary Outcome Measures :
  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: length of study plus 30 days ]
    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 :
  1. Progression Free Survival (PFS) [ Time Frame: 2 years ]
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  2. Number of Patients With an Overall Response Rate (ORR) of PR or CR [ Time Frame: 1 year ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  3. Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours ]
  4. Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours ]
  5. AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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): NCT01059071

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
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Giselle Sholler
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
Study Chair: Giselle Sholler, MD The Spectrum Health Group
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Giselle Sholler, Study Chair, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT01059071     History of Changes
Other Study ID Numbers: NMTRC 002
First Posted: January 29, 2010    Key Record Dates
Results First Posted: June 20, 2016
Last Update Posted: October 27, 2016
Last Verified: September 2016

Keywords provided by Giselle Sholler, Spectrum Health Hospitals:
Refractory Neuroblastoma
Relapsed neuroblastoma

Additional relevant MeSH terms:
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Etoposide phosphate
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Ornithine Decarboxylase Inhibitors