Clinical trial NCT02395666: Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission
Official title: A Phase II Preventative Trial of DFMO (Eflornithine HCl) as a Single Agent in Patients With High Risk Neuroblastoma in Remission
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma
Keywords: Neuroblastoma in remission
Relapsed Neuroblastoma
Refractory Neuroblastoma
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: Beat NB Cancer Foundation
name: Because of Ezra
name: K C Pharmaceuticals Inc.
First posted: 2015-03-23
Enrollment: 140
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this research study is to evaluate a new investigational drug to prevent reoccurrence of neuroblastoma that is in remission. This study drug is called DFMO. The objectives of this study will be to monitor for safety and look at efficacy of DFMO.

The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO may continue on treatment up to 27 cycles with the expectation that there will be an overall clinical benefit.

The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), meta-iodobenzylguanidine (MIBG) scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO.

The proposed dosing regimen is an oral dose of DFMO tablets two times a day for each day while on study. There will be 27 cycles. Each cycle will be 28 days in length.


Eligibility criteria: Inclusion Criteria:

* Age: 0-21 years at the time of diagnosis.
* Diagnosis: histologic verification at either the time of original diagnosis or a previous relapse of high risk neuroblastoma.
* Disease Status: Neuroblastoma that is in remission
* First dose of study medication must be greater than 30 days from completion of cytotoxic and antibody therapy and less than 120 days from previous therapy
* A negative serum or urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
* Both male and female post-pubertal study subjects need to agree to use one of the more effective birth control methods during treatment and for six months after treatment is stopped. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonorgestrel implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
* Absolute Neutrophil Count (ANC) \> 500/μl and platelet count \>50,000/μl
* Organ Function Requirements: Subjects must have adequate liver function as defined by:

  * Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) \<10x upper limit of normal
  * Serum bilirubin must be ≤ 2.0 mg/dl
  * Serum creatinine based on age/gender
* Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria:

* Lansky score \< 60%
* Body Surface Area (BSA) (m2) of \<0.25
* 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 the effects of prior chemotherapy (hematological and bone marrow suppression effects).
* 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: Percentage of Participants With Overall Survival (OS)
timeFrame: 2 Years
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: 2 years
measure: Test the Association of Survival With ODC1 Genotype
timeFrame: 2 years
measure: Peak Plasma Concentration (Cmax)
timeFrame: Samples drawn at 5 timepoints: (0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose) on two different days
measure: Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
measure: Time to Reach Peak Plasma Concentration (Tmax)
timeFrame: 0 (pre dose), 30min, 1 hour, 3 hours, and 6 hours post-dose on two different days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Hartford
country: United States
facility: Connecticut Children's Hospital
state: Connecticut
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: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Boston
country: United States
facility: Tufts Medical Center
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 on 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: Cardinal Glennon Children's Medical Center
state: Missouri
city: Bronx
country: United States
facility: The Children's Hospital at Montefiore
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center and Children's Hospital
state: Pennsylvania
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
Study officials:
affiliation: Beat Childhood Cancer
name: Giselle Saulnier-Sholler, MD
role: STUDY_CHAIR
References:
citation: Urban-Wojciuk Z, Graham A, Barker K, Kwok C, Sbirkov Y, Howell L, Campbell J, Woster PM, Poon E, Petrie K, Chesler L. The biguanide polyamine analog verlindamycin promotes differentiation in neuroblastoma via induction of antizyme. Cancer Gene Ther. 2022 Jul;29(7):940-950. doi: 10.1038/s41417-021-00386-6. Epub 2021 Sep 14.
citation: Batth IS, Dao L, Satelli A, Mitra A, Yi S, Noh H, Li H, Brownlee Z, Zhou S, Bond J, Wang J, Gill J, Sholler GS, Li S. Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients. Int J Cancer. 2020 Dec 15;147(12):3550-3559. doi: 10.1002/ijc.33140. Epub 2020 Jun 23.
citation: Lewis EC, Kraveka JM, Ferguson W, Eslin D, Brown VI, Bergendahl G, Roberts W, Wada RK, Oesterheld J, Mitchell D, Foley J, Zage P, Rawwas J, Rich M, Lorenzi E, Broglio K, Berry D, Saulnier Sholler GL. A subset analysis of a phase II trial evaluating the use of DFMO as maintenance therapy for high-risk neuroblastoma. Int J Cancer. 2020 Dec 1;147(11):3152-3159. doi: 10.1002/ijc.33044. Epub 2020 May 24.