Full Trial Info on ClinicalTrials.gov
DFMO is an oral drug that inhibits ODC and polyamines which are critical in cancer growth and therefore present a therapeutic target for the treatment and prevention of recurrence of NB and other types of cancer.
Open Sites:
Orlando- Arnold Palmer Hospital for Children
M.D. Anderson Cancer Center Orlando
North Carolina- Levine Children's Hospital and Carolinas Medical Center
Michigan- Helen DeVos Children’s Hospital
Connecticut Children’s Medical Center
Kansas City- Children's Mercy Hospitals and Clinics - in progress of opening
Oncology Children's Hospital of Orange County
Research Articles:
Ornithine decarboxylase inhibition by alpha-difluoromethylornithine activates opposing signaling pathways via phosphorylation of both Akt/protein kinase B and p27Kip1 in neuroblastoma
Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells
Objectives:
Primary
To determine the safety, tolerability and maximum tolerated dose (MTD) of DFMO as a single agent and in combination with etoposide in pediatric and young adult patients with refractory or recurrent neuroblastoma
Secondary
To evaluate the activity of DFMO as a single agent and in combination with etoposide based on:
- Progression free survival (PFS)
- Overall response rate (ORR)
To evaluate the pharmacokinetics (PK) of DFMO as single agent
Methodology:
DFMO is an open label, multicenter, dose escalation study in patients with refractory or recurrent neuroblastoma.
Patients: 4 cohorts, 3-6 pts. per cohort
Cycle1: Patient will take DFMO by mouth 2 times a day for 21 days
Cycle 2-5: Patient will take DFMO by mouth 2 times a day for 21 days and Etoposide by mouth 1 time a day for the first 14 days
The following will be monitored:
- Physical examination (including height and weight)
- BSA calculation (from body weight and height);
- Vital signs, including temperature, pulse rate, and blood pressure
- Blood tests and Urine VMA/HVA
- Adverse Events
- CT/MRI, MIBG, Bone Marrow, and Audiogram
Eligibility
Inclusion:
- 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 or evaluable disease, including at least one of the following: Measureable 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 and ALT <10x upper limit of normal
Serum bilirubin must be ≤ 2.0 mg/dl
Serum creatinine must be ≤ 3 mg/dl x upper limit of normal
Exclusion:
- Life expectancy <2 months or Lansky <30%
- Investigational drug therapy
- Infection not under control
To Participate, Contact:
Study Chair
Giselle Sholler, M.D.
616-234-5495
Email
Program Manager
Genevieve Bergendahl, R.N.
616-234-5707
Email
