Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

Phase II Trial of Eflornithine (DFMO) and Etoposide for Relapsed/Refractory Neuroblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04301843
• Other study ID #: BCC015
• Status: Recruiting
• Phase: Phase 2
• Start date: September 25, 2020
• Est. completion date: October 1, 2033

Study information

• Verified date: April 2024
• Source: Milton S. Hershey Medical Center
• Contact: Genevieve Bergendahl, MSN
• Phone: 7175310003
• Email: gbergendahl[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 131
• Est. completion date: October 1, 2033
• Est. primary completion date: October 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 31 Years

Eligibility

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: 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: Adequate renal function defined as (perform one of the following):

Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or greater or a serum creatinine based on age/gender

• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients 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.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

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

Locations

Country	Name	City	State
Canada	Montreal Children's Hospital	Montréal	Quebec
Canada	UHC Sainte-Justine	Montréal	Quebec
Canada	CHUQ	Quebec City	Quebec
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Augusta University Health	Augusta	Georgia
United States	Dell Children's Blood and Cancer Center	Austin	Texas
United States	University of Alabama, Children's Alabama	Birmingham	Alabama
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Cleveland Clinic Children's	Cleveland	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Hospital	Hartford	Connecticut
United States	Penn State Milton S. Hershey Medical Center and Children's Hospital	Hershey	Pennsylvania
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Louisville	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital and Clinics of Minnesota	Minneapolis	Minnesota
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	UCSF Benioff Children's Hospital Oakland-	Oakland	California
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Hasbro Children's Hospital	Providence	Rhode Island
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Rady Children's Hospital	San Diego	California
United States	St. Joseph's Children's Hospital	Tampa	Florida

Sponsors (4)

Lead Sponsor	Collaborator
Giselle Sholler	Beat NB Cancer Foundation, K C Pharmaceuticals Inc., Team Parker for Life

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with event free survival (EFS) during study	To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon: o Event free survival (EFS) from time of enrollment.	2 years plus 5 years follow up
Secondary	Length of time that participants experience Overall Survival (OS)	To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon: o Overall Survival (OS) from time of enrollment.	7 years
Secondary	Determine the Overall Response Rate (ORR) of Participants using INSS Response Evaluation Criteria.	To evaluate the efficacy of difluoromethylornithine (DFMO) in combination with etoposide in patients with relapsed/refractory neuroblastoma, based upon: o Response Rate for patients with active disease (Arm 3) using International Neuroblastoma Staging System (INSS) Response Evaluation Criteria.	2 years
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	To monitor the safety and tolerability profile of difluoromethylornithine (DFMO) in combination with etoposide in pediatric and young adult patients with relapsed/refractory neuroblastoma.	2 years plus 30 days

External Links

•   Beat Childhood Cancer Consortium website