Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

NCT ID: NCT04301843

Last Updated: 2025-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

131 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-25

Study Completion Date

2033-10-01

Brief Summary

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Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.

Detailed Description

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Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study in combination with etoposide for subjects with relapsed/refractory neuroblastoma.

In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.

Subjects will be evaluated in 3 arms:

• Arm 1: Subjects who show no active disease after receiving any additional therapy for neuroblastoma that was refractory to standard induction/consolidation therapy.

Refractory: Subjects with progressive disease on upfront therapy OR did not have at least PR on induction OR required additional second line therapy to achieve remission who are now in first remission.

* Arm 2: Subjects who have previously relapsed and currently show no active disease (in CR2 or greater).
* Arm 3: Subjects who are relapsed or refractory with active disease.- CLOSED TO ENROLLMENT

Conditions

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Neuroblastoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Eflornithine (DFMO)

In this study subjects will receive six 21-day cycles of Etoposide and DFMO followed by an additional 630 days of DFMO alone.

Etoposide will be given at 50 mg/m2/dose PO daily for the first 14 days of each 21 days until 6 cycles of etoposide are completed.

DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.

Group Type EXPERIMENTAL

Eflornithine

Intervention Type DRUG

DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.

Interventions

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Eflornithine

DFMO (difluoromethylornithine) will be given at a dose of 1000 mg/m2 BID on each day of study.

Intervention Type DRUG

Other Intervention Names

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DFMO difluoromethylornithine

Eligibility Criteria

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Inclusion Criteria

* All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
* All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
* Specific Criteria by Arm:

Arms 1 and 2:

Subjects with no active disease:

i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease).

o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required.

ii. No evidence of disease metastatic to bone marrow.

Arm 3 \[CLOSED TO ENROLLMENT\]:

Measurable or evaluable disease, including at least one of the following:

Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.

* Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.
* Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines:

1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea).
2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor.
3. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair.
4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells.
5. Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody.
6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
7. Stem Cell Transplant:

1. Allogeneic: No evidence of active graft vs. host disease
2. Allo/Auto: ≥ 2 months must have elapsed since transplant.
8. MIBG Therapy: At least 8 weeks since treatment with MIBG therapy
* Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher.
* Life expectancy \> 2 months
* All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.
* Subjects must have adequate organ functions at the time of registration:

* Hematological: Total absolute neutrophil count ANC ≥750/μL
* Liver: Subjects must have adequate liver function as defined by AST and ALT \<5x upper limit of normal (Normal=45), Bilirubin \<1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen.
* Renal: Estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70.

The Bedside Schwartz equation is: \[(0.413) X (Height in cm)\] / SCr

* Subjects of childbearing potential must have a negative pregnancy test. Subjects of childbearing potential must agree to use an effective birth control method. Subjects who are lactating must agree to stop breast-feeding.
* Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).

Exclusion Criteria

* BSA of \<0.25 m2.
* Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
* Subjects that received a dose of DFMO in combination with etoposide are not eligible.
* 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 hematological and bone marrow suppression effects of prior chemotherapy.
* 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.
Maximum Eligible Age

31 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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K C Pharmaceuticals Inc.

INDUSTRY

Sponsor Role collaborator

Beat NB Cancer Foundation

OTHER

Sponsor Role collaborator

Team Parker for Life

UNKNOWN

Sponsor Role collaborator

USWM, LLC

UNKNOWN

Sponsor Role collaborator

Giselle Sholler

OTHER

Sponsor Role lead

Responsible Party

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Giselle Sholler

Chair, Beat Childhood Cancer

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Giselle Sholler, MD

Role: STUDY_CHAIR

Beat Childhood Cancer

Locations

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University of Alabama, Children's Alabama

Birmingham, Alabama, United States

Site Status RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Site Status RECRUITING

UCSF Benioff Children's Hospital Oakland-

Oakland, California, United States

Site Status RECRUITING

Rady Children's Hospital

San Diego, California, United States

Site Status RECRUITING

Connecticut Children's Hospital

Hartford, Connecticut, United States

Site Status RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Site Status RECRUITING

St. Joseph's Children's Hospital

Tampa, Florida, United States

Site Status RECRUITING

Augusta University Health

Augusta, Georgia, United States

Site Status RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status RECRUITING

University of Louisville

Louisville, Kentucky, United States

Site Status RECRUITING

Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Site Status RECRUITING

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status RECRUITING

Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status RECRUITING

Levine Children's Hospital

Charlotte, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic Children's

Cleveland, Ohio, United States

Site Status RECRUITING

Penn State Milton S. Hershey Medical Center and Children's Hospital

Hershey, Pennsylvania, United States

Site Status RECRUITING

Hasbro Children's Hospital

Providence, Rhode Island, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status NOT_YET_RECRUITING

Dell Children's Blood and Cancer Center

Austin, Texas, United States

Site Status RECRUITING

Children's Medical Center Dallas

Dallas, Texas, United States

Site Status RECRUITING

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Site Status RECRUITING

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

UHC Sainte-Justine

Montreal, Quebec, Canada

Site Status RECRUITING

CHUQ

Québec, Quebec, Canada

Site Status RECRUITING

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, Canada

Site Status RECRUITING

Countries

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United States Canada

Central Contacts

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BCC Enroll

Role: CONTACT

7175310003

Facility Contacts

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Bridget Tate

Role: primary

Susan Hall

Role: primary

501-364-2760

Group Contact

Role: primary

Sherri Brandsen

Role: primary

858-966-8155

Nicole McCracken

Role: primary

860-545-9337

Michelle Pellet

Role: primary

321-841-8588

Jennifer Manns, RN

Role: primary

813-357-0849

Kimberly Gray

Role: primary

Andrea Siu, MPH

Role: primary

808-535-7169

Jennifer Miller

Role: primary

Mary Beth Readwin

Role: primary

616-267-0334

Nel Siemsen

Role: primary

612-813-5913

Nicole Harvey

Role: primary

816-302-6893

Gina Martin

Role: primary

314-268-4000

Sherri Mayans

Role: primary

Jotnyce Green

Role: primary

980-442-2356

Luba Platt

Role: primary

Suzanne Treadway

Role: primary

Christopher Bouressa

Role: primary

Shanta Salzar, MD

Role: primary

843-792-2957

Rhea Robinson, RN

Role: primary

512-628-1902

Caitlyn Ambrose

Role: primary

Sabrina Wigginton

Role: primary

Ashley Hain

Role: primary

Krista Mueller

Role: primary

Dominique Lafreniere

Role: primary

Guillaume Leblanc

Role: primary

Valérie-Ève Julien

Role: primary

Cassandra Leblanc Desrochers

Role: primary

Related Links

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https://research.beatcc.org/

Beat Childhood Cancer Consortium website

Other Identifiers

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BCC015

Identifier Type: -

Identifier Source: org_study_id

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