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

NCT02030964 | Completed Phase 1 DMC

• 2 other identifiers: N2012-01P01CA081403
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 13

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Approximately 1 year

Study Arms (1)

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.

Drug: DFMO; Drug: Celecoxib; Drug: Cyclophosphamide; Drug: Topotecan

Interventions

DFMO DRUG

Also known as: Difluoromethylornithine

DFMO, Celecoxib, Cyclophosphamide & Topotecan

Celecoxib DRUG

Also known as: Celebrex

DFMO, Celecoxib, Cyclophosphamide & Topotecan

Cyclophosphamide DRUG

Also known as: Cytoxan

DFMO, Celecoxib, Cyclophosphamide & Topotecan

Topotecan DRUG

Also known as: Hycamtin

DFMO, Celecoxib, Cyclophosphamide & Topotecan

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New Approaches to Neuroblastoma Therapy Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

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

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Childrens Hospital Boston, Dana-Farber Cancer Institute.

Boston, Massachusetts, 02115, United States

Location

C.S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Sydney Childrens Hospital KCC

Randwick, 2031, Australia

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Eflornithine; Celecoxib; Cyclophosphamide; Topotecan

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Camptothecin; Alkaloids

Study Officials

• Michael Hogarty, MD

  Children's Hospital of Philadelphia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2014
• First Posted: January 9, 2014
• Study Start: January 16, 2014
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

AU (1); US (11); CA (1)