Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
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).
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide|
- Number of Participants With Adverse Events as a Measure of Safety and Tolerability [ Time Frame: length of study plus 30 days ]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
- Progression Free Survival (PFS) [ Time Frame: 2 years ]Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Number of Patients With an Overall Response Rate (ORR) of PR or CR [ Time Frame: 1 year ]Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
- Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours ]
- Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours ]
- AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing. [ Time Frame: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours ]
|Study Start Date:||February 2010|
|Study Completion Date:||May 2015|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
|Experimental: DFMO and Etoposide||
Escalating doses of DFMO in a 3 +3 cohort design.
DFMO at current cohort Dose Level orally each day for 21 day cycles
Dose level 1: 500 mg/m2 PO BID Dose level 2: 750 mg/m2 PO BID Dose level 3:1000 mg/m2 PO BID Dose level 4:1500 mg/m2 PO BID
Other Name: DifluoromethylornithineDrug: Etoposide
Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01059071
|United States, California|
|Children's Hospital of Orange County|
|Orange, California, United States, 92868|
|United States, Connecticut|
|Connecticut Children's Hospital|
|Hartford, Connecticut, United States, 06106|
|United States, Florida|
|Arnold Palmer Hospital for Children- MD Anderson|
|Orlando, Florida, United States, 32806|
|United States, Michigan|
|Helen DeVos Children's Hospital|
|Grand Rapids, Michigan, United States, 49503|
|United States, Missouri|
|Children's Mercy Hospitals and Clinics|
|Kansas City, Missouri, United States, 64108|
|United States, North Carolina|
|Levine Children's Hospital|
|Charlotte, North Carolina, United States, 28204|
|United States, Vermont|
|Burlington, Vermont, United States, 05401|
|Study Chair:||Giselle Sholler, MD||The Spectrum Health Group|