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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01059071
Recruitment Status : Completed
First Posted : January 29, 2010
Results First Posted : June 20, 2016
Last Update Posted : April 22, 2022
Sponsor:
Collaborators:
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Tracking Information
First Submitted Date  ICMJE January 26, 2010
First Posted Date  ICMJE January 29, 2010
Results First Submitted Date  ICMJE May 11, 2016
Results First Posted Date  ICMJE June 20, 2016
Last Update Posted Date April 22, 2022
Study Start Date  ICMJE February 2010
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2016)
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
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2010)
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 [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
  • 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
  • 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.
  • 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 ]
  • 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 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2010)
  • 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 ]
  • To evaluate the activity of DFMO as a single agent and in combination with etoposide in these tumor types based on: Overall response rate (ORR) [ Time Frame: 1 year ]
  • To evaluate the pharmacokinetics (PK) of DFMO as single agent [ Time Frame: Cycle 1 Day 1 and 8 ]
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
Official Title  ICMJE A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
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).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: DFMO and Etoposide
Interventions:
  • Drug: DFMO
  • Drug: Etoposide
Publications * Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One. 2015 May 27;10(5):e0127246. doi: 10.1371/journal.pone.0127246. eCollection 2015.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2016)
21
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2010)
24
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01059071
Other Study ID Numbers  ICMJE NMTRC 002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Wake Forest University Health Sciences
Original Responsible Party Giselle Sholler, MD, University of Vermont
Current Study Sponsor  ICMJE Wake Forest University Health Sciences
Original Study Sponsor  ICMJE University of Vermont
Collaborators  ICMJE
  • Cancer Prevention Pharmaceuticals, Inc.
  • University of Arizona
  • University of Hawaii
Investigators  ICMJE
Study Chair: Giselle Sholler, MD Beat Childhood Cancer at Atrium Health
PRS Account Wake Forest University Health Sciences
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP