Clinical trial NCT02679144: Neuroblastoma Maintenance Therapy Trial
Official title: NMTT- Neuroblastoma Maintenance Therapy Trial Using Difluoromethylornithine (DFMO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neuroblastoma
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: Beat NB Cancer Foundation
name: Team Parker for Life
First posted: 2016-02-10
Enrollment: 441
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Difluoromethylornithine (DFMO) will be used in an open label, single agent, multicenter, study for patients with neuroblastoma in remission. In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 750 mg/m2 ± 250 mg/m2 BID (strata 1, 2, 3, and 4) OR 2500 mg/m2 BID (stratum 1B) on each day of study. This study will focus on the use of DFMO in high risk neuroblastoma patients that are in remission as a strategy to prevent recurrence.


Eligibility criteria: Inclusion Criteria:

* All patients must have a pathologically confirmed diagnosis of neuroblastoma, \< 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
* All patients must be in complete remission (CR):

  1. No evidence of residual disease on scan
  2. No evidence of disease metastatic to bone marrow.
* Specific Criteria by Stratum:

Stratum 1/1B: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including:

intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;.

All subjects on Stratum 1/B must have also met the following criteria:

• A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy.

Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1.

Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy.

Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).

* Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:

  * Tumor imaging studies including
  * Bilateral bone marrow aspirates and biopsy
  * This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment.
* Timing from prior therapy:

Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy.

Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.

* Patients must have a Lansky or Karnofsky Performance Scale score of \> 50% and patients must have a life expectancy of ≥ 2 months.
* All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.
* Patients must have adequate organ functions at the time of registration:

  * Hematological: Total absolute phagocyte count ≥1000/μL
  * Liver: Subjects must have adequate liver function
  * Renal: Adequate renal function
* 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 (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).

Exclusion Criteria:

* BSA (Body Surface Area) of \<0.25 m2.
* 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.

Primary outcomes:
measure: Number of participants with event free survival (EFS) during study.
timeFrame: 2 years
Secondary outcomes:
measure: Length of time that participants experience Overall Survival (OS)
timeFrame: 7 years
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 2 years
measure: Peak Plasma Concentration (Cmax)
timeFrame: 1 year
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 1 year
measure: Time to reach Peak Plasma Concentration (Tmax)
timeFrame: 1 year
measure: Number of participants with ODC (Ornithine decarboxylase) single nucleotide polymorphisms.
timeFrame: 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Children's of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland-
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Denver
country: United States
facility: Rocky Mountain Pediatric Hematology
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Hospital
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital Johns Hopkins Medicine
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Children's Hospital
state: Florida
city: Augusta
country: United States
facility: Augusta University Health
state: Georgia
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Boise
country: United States
facility: St. Lukes
state: Idaho
city: Chicago
country: United States
facility: Rebecca McFall
state: Illinois
city: Lexington
country: United States
facility: Kentucky Children's Hospital
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School Worcester
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospital and Clinics of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Gina Martin
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Children's
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Randall Children's Hospital
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center and Children's Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Hasbro Children's Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Monroe Carrell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Blood and Cancer Center
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Cancer and Hematology Centers
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John's
country: Canada
facility: Janesway Children's Health and Rehabilitation Centre
state: Newfoundland and Labrador
city: Montreal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Montréal
country: Canada
facility: UHC Sainte-Justine
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie-CHUS
state: Quebec
Study officials:
affiliation: Beat Childhood Cancer at Atrium Health
name: Giselle Sholler, MD
role: STUDY_CHAIR
References: