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

NCT ID: NCT02030964

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-16
• Study Completion Date: 2023-12-30

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.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DFMO, Celecoxib, Cyclophosphamide & Topotecan

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.

Group Type: EXPERIMENTAL

DFMO

Intervention Type: DRUG

Celecoxib

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Interventions

DFMO

Intervention Type: DRUG

Celecoxib

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Topotecan

Intervention Type: DRUG

Other Intervention Names

Difluoromethylornithine; Celebrex; Cytoxan; Hycamtin

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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

New Approaches to Neuroblastoma Therapy Consortium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Hogarty, MD

Role: STUDY_CHAIR

Children's Hospital of Philadelphia

Locations

Children's Hospital Los Angeles

Los Angeles, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Children Hospital of Colorado

Aurora, Colorado, United States

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, United States

University of Chicago Comer Children's Hospital

Chicago, Illinois, United States

Childrens Hospital Boston, Dana-Farber Cancer Institute.

Boston, Massachusetts, United States

C.S Mott Children's Hospital

Ann Arbor, Michigan, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Sydney Childrens Hospital KCC

Randwick, , Australia

Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Australia; Canada

Other Identifiers

P01CA081403

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N2012-01

Identifier Type: -

Identifier Source: org_study_id