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: 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 ] [ Designated as safety issue: Yes ]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
- To evaluate the activity of DFMO as a single agent and in combination with etoposide in these tumor types based on: Progression free survival (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Determine the Overall Response Rate (ORR) of Participants using RECIST criteria Determine the Overall Response Rate (ORR) of Participants using RECIST criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- To evaluate the pharmacokinetics (PK) of DFMO as single agent [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Biology studies to include: effect on polyamine depletion, ODC activity, genomic analysis of cells pre- and post- treatment, correlation of in vitro response to in vivo response, flow cytometry of tumor burden in bone marrow and biomarker development [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||February 2010|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
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
|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|