Clinical Trial: NCT02030964 - My Cancer Genome

NCT02030964

Description:

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.

Related Conditions:

Neuroblastoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02030964

Trial Eligibility

Document

Title

Brief Title: N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan
Official Title: N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma

Clinical Trial IDs

ORG STUDY ID: N2012-01
SECONDARY ID: P01CA081403
NCT ID: NCT02030964

Conditions

Neuroblastoma

Interventions

Drug	Synonyms	Arms
DFMO	Difluoromethylornithine	DFMO, Celecoxib, Cyclophosphamide & Topotecan
Celecoxib	Celebrex	DFMO, Celecoxib, Cyclophosphamide & Topotecan
Cyclophosphamide	Cytoxan	DFMO, Celecoxib, Cyclophosphamide & Topotecan
Topotecan	Hycamtin	DFMO, Celecoxib, Cyclophosphamide & Topotecan

Purpose

Trial Arms

Name	Type	Description	Interventions
DFMO, Celecoxib, Cyclophosphamide & Topotecan	Experimental	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.	DFMO Celecoxib Cyclophosphamide Topotecan

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.

Maximum Eligible Age:	30 Years
Minimum Eligible Age:	2 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Number of participants with adverse events as a measure of safety and tolerability.
Time Frame:	Approximately 1 year
Safety Issue:
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.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	New Approaches to Neuroblastoma Therapy Consortium

Last Updated

January 20, 2021

Clinical Trials /

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