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N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan (DFMO)

Primary Purpose

Neuroblastoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DFMO
Celecoxib
Cyclophosphamide
Topotecan
Sponsored by
New Approaches to Neuroblastoma Therapy Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma

Eligibility Criteria

2 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must be > 2 years and < 30 years of age when registered on study.
  • Patients must have recurrent/progressive high-risk neuroblastoma, refractory high-risk neuroblastoma that had less than a partial response to standard treatment or persistent high-risk neuroblastoma that had at least a partial response to standard treatment.
  • All patients must have at least ONE site of evaluable disease.
  • Patients must have adequate heart, kidney, liver and bone marrow function.
  • Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
  • Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.

Exclusion Criteria:

  • Females of childbearing potential that do not have a negative pregnancy test.
  • Patients that are pregnant, breast feeding, or unwilling to use effective contraception during the study
  • Patients status post allogeneic stem cell transplant.
  • Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
  • Patients with disease of any major organ system that would compromise their ability to withstand therapy.
  • Patients who are on hemodialysis.
  • Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria.
  • Patients with active bleeding of the GI tract or patients who have symptoms associated with stomach irritation (known as gastritis).
  • Patients who have had a seizure within 12 months prior to enrollment and patients receiving anti-convulsant therapy for a seizure disorder.
  • Patients with known Aspirin-Hypersensitivity triad (asthma, allergic rhinitis, ASA hypersensitivity).
  • Patients with known hypersensitivity to celecoxib or other NSAIDs, aspirin or sulfonamides.

Sites / Locations

  • Children's Hospital Los Angeles
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • Children Hospital of Colorado
  • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
  • University of Chicago Comer Children's Hospital
  • Childrens Hospital Boston, Dana-Farber Cancer Institute.
  • C.S Mott Children's Hospital
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia
  • Cook Children's Medical Center - Fort Worth
  • Children's Hospital and Regional Medical Center - Seattle
  • Sydney Childrens Hospital KCC
  • Hospital for Sick Children

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DFMO, Celecoxib, Cyclophosphamide & Topotecan

Arm Description

Reconstituted DFMO powder by mouth for 14 days and celecoxib capsule by mouth daily in each cycle. Cyclophosphamide and Topotecan IV on days 8-12 in cycle 1 and days 1-5 of cycles 2-17. Patients may continue for up to 17 cycles as long as therapy is tolerated (no DLT) and disease progression does not occur (SD or better). *Cycle 1 will include a 7 day lead-in with DFMO and celecoxib to deplete tumor polyamines.

Outcomes

Primary Outcome Measures

Number of participants with adverse events as a measure of safety and tolerability.
The standard 3+3 design for dose escalation will be utilized. 3-6 patients will enroll at each of 4 dose levels, but enrollment to a dosing cohort will cease after observation of DLTs in 2 or more patients. A minimum of 2 to a maximum of 24 patients will be enrolled assuming all 4 dose levels require 6 patients before an MTD is determined. A total of 12 patients may be enrolled at the study defined MTD (including those used to define the MTD) to provide additional adverse event data for safety evaluation.

Secondary Outcome Measures

Full Information

First Posted
January 2, 2014
Last Updated
January 30, 2023
Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02030964
Brief Title
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan
Acronym
DFMO
Official Title
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will combine an oral drug called DFMO with celecoxib (also oral) and two IV chemotherapy medicines called cyclophosphamide and topotecan. To find the highest dose of DFMO that can be given with celecoxib, cyclophosphamide and topotecan without causing severe side effects. To find out the side effects seen by giving DFMO at different dose levels with celecoxib, cyclophosphamide and topotecan. To measure the levels of DFMO in the blood at different dose levels. To determine if your tumor gets smaller after treatment with DFMO, celecoxib, cyclophosphamide and topotecan. To determine if specific gene changes in you or your tumor makes you more prone to side effects or affects your tumor's response to the combination of DFMO, celecoxib, cyclophosphamide and topotecan. To determine if the amount of normal chemicals in your body called polyamines go down in response to DFMO, celecoxib, cyclophosphamide and topotecan, and whether you are more likely to have a good response to the treatment if they do.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
DFMO, Celecoxib, Cyclophosphamide & Topotecan
Arm Type
Experimental
Arm Description
Reconstituted DFMO powder by mouth for 14 days and celecoxib capsule by mouth daily in each cycle. Cyclophosphamide and Topotecan IV on days 8-12 in cycle 1 and days 1-5 of cycles 2-17. Patients may continue for up to 17 cycles as long as therapy is tolerated (no DLT) and disease progression does not occur (SD or better). *Cycle 1 will include a 7 day lead-in with DFMO and celecoxib to deplete tumor polyamines.
Intervention Type
Drug
Intervention Name(s)
DFMO
Other Intervention Name(s)
Difluoromethylornithine
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Celebrex
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Type
Drug
Intervention Name(s)
Topotecan
Other Intervention Name(s)
Hycamtin
Primary Outcome Measure Information:
Title
Number of participants with adverse events as a measure of safety and tolerability.
Description
The standard 3+3 design for dose escalation will be utilized. 3-6 patients will enroll at each of 4 dose levels, but enrollment to a dosing cohort will cease after observation of DLTs in 2 or more patients. A minimum of 2 to a maximum of 24 patients will be enrolled assuming all 4 dose levels require 6 patients before an MTD is determined. A total of 12 patients may be enrolled at the study defined MTD (including those used to define the MTD) to provide additional adverse event data for safety evaluation.
Time Frame
Approximately 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must be > 2 years and < 30 years of age when registered on study. Patients must have recurrent/progressive high-risk neuroblastoma, refractory high-risk neuroblastoma that had less than a partial response to standard treatment or persistent high-risk neuroblastoma that had at least a partial response to standard treatment. All patients must have at least ONE site of evaluable disease. Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study. Patients with other ongoing serious medical issues must be approved by the study chair prior to registration. Exclusion Criteria: Females of childbearing potential that do not have a negative pregnancy test. Patients that are pregnant, breast feeding, or unwilling to use effective contraception during the study Patients status post allogeneic stem cell transplant. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. Patients with disease of any major organ system that would compromise their ability to withstand therapy. Patients who are on hemodialysis. Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture and biopsy negative in suspected radiographic lesions and meet other organ function criteria. Patients with active bleeding of the GI tract or patients who have symptoms associated with stomach irritation (known as gastritis). Patients who have had a seizure within 12 months prior to enrollment and patients receiving anti-convulsant therapy for a seizure disorder. Patients with known Aspirin-Hypersensitivity triad (asthma, allergic rhinitis, ASA hypersensitivity). Patients with known hypersensitivity to celecoxib or other NSAIDs, aspirin or sulfonamides.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Hogarty, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027-0700
Country
United States
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Children Hospital of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago Comer Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Childrens Hospital Boston, Dana-Farber Cancer Institute.
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
C.S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104-4318
Country
United States
Facility Name
Cook Children's Medical Center - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Children's Hospital and Regional Medical Center - Seattle
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Sydney Childrens Hospital KCC
City
Randwick
ZIP/Postal Code
2031
Country
Australia
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan

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