Clinical trial NCT01059071: Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
Official title: A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Keywords: Refractory Neuroblastoma
Relapsed neuroblastoma
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: Cancer Prevention Pharmaceuticals, Inc.
name: University of Arizona
name: University of Hawaii
First posted: 2010-01-29
Enrollment: 21
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to evaluate a new investigational drug to treat neuroblastoma. This study drug is called DFMO. The objectives of this study will be to monitor for safety and to find a maximum tolerated dose in this population. A secondary objective will be to 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 and/or etoposide may continue on treatment 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), 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, and later combined with an already approved drug, etoposide.

The proposed dosing regimen is an oral dose of DFMO two times a day for each day while on study. There will be 5 cycles. Each cycle will be 21 days in length. The first cycle will be DFMO alone. In the second cycle etoposide will be added in and will be given orally once a day for the first 14 days of each cycle (cycles 2-5).


Eligibility criteria: Inclusion Criteria:

* Age: 0-21 years at the time of diagnosis.
* Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
* Disease Status: Refractory or relapsed neuroblastoma
* Measurable disease, including at least one of the following:

Measurable tumor \>10mm by CT or MRI A positive MIBG and abnormal urinary catecholamine levels Positive bone marrow biopsy/aspirate.

* Current disease state must be one for which there is currently no known curative therapy.
* A negative urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
* Patients without bone marrow metastases must have an ANC \> 500/μl and platelet count \>50,000/μl
* Organ Function Requirements Subjects must have adequate liver function as defined by AST or ALT \<10x normal Serum bilirubin must be ≤ 2.0 mg/dl Serum creatinine must be ≥ 1.5 mg/dl
* 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:

* Life expectancy \<2 months or Lansky score \<30%
* 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 Adverse Events as a Measure of Safety and Tolerability
timeFrame: length of study plus 30 days
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Number of Patients With an Overall Response Rate (ORR) of PR or CR
timeFrame: 1 year
measure: Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
timeFrame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
measure: Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
timeFrame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
measure: AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
timeFrame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
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- MD Anderson
state: Florida
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Burlington
country: United States
facility: UVM/FAHC
state: Vermont
Study officials:
affiliation: Beat Childhood Cancer at Atrium Health
name: Giselle Sholler, MD
role: STUDY_CHAIR
References:
citation: Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One. 2015 May 27;10(5):e0127246. doi: 10.1371/journal.pone.0127246. eCollection 2015.