Pediatric Precision Laboratory Advanced Neuroblastoma Therapy
- Conditions
- Neuroblastoma
- Interventions
- Registration Number
- NCT02559778
- Lead Sponsor
- Giselle Sholler
- Brief Summary
A prospective open label, multicenter study to evaluate the feasibility and acute toxicity of using molecularly guided therapy in combination with standard therapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard Immunotherapy with DFMO DFMO One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days. Standard Immunotherapy without DFMO dasatinib One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days. Standard Immunotherapy without DFMO Ceritinib One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days. Standard Immunotherapy without DFMO sorafenib One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days. Standard Immunotherapy without DFMO vorinostat One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days. Standard Immunotherapy with DFMO Ceritinib One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days. Standard Immunotherapy with DFMO dasatinib One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days. Standard Immunotherapy with DFMO sorafenib One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days. Standard Immunotherapy with DFMO vorinostat One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days.
- Primary Outcome Measures
Name Time Method Number of days from start of therapy to date of first relapse Up to 8 years To measure the response of treatments chosen based on:
• Event free survival (EFS)Number of subjects that have a targeted agent chosen for treatment. 2 years At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:
1. Subject has a targeted agent identified
2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
3. Subject is not removed from study due to targeted agent drug related toxicity.Number of subjects that receive 75% of dosing of medications while on study protocol during cycles 3-6. 2 years At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:
1. Subject has a targeted agent identified
2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
3. Subject is not removed from study due to targeted agent drug related toxicity.
- Secondary Outcome Measures
Name Time Method Number of days that subjects remain alive 3 years plus 5 years follow up To measure the response of treatments chosen based on:
* Overall response rate (ORR) after induction therapy
* Overall survival (OS)Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 3 years To compare toxicity effects of difluoromethylornithine (DFMO) in combination with Dinutuximab/GM-CSF/IL-2 and isotretinoin versus Dinutuximab/GM-CSF/IL-2 and isotretinoin alone.
Overall Response Rate (ORR) of Participants by the presence of radiologically assessable disease by cross-sectional CT or MRI imaging and/or by MIBG or PET scans. Up to 8 years To measure the response of treatments chosen based on:
• Overall response rate (ORR) after induction therapyAmount of pain medicine required by Arm A versus Arm B 3 years To compare level of pain medicine needed during immunotherapy in patients receiving difluoromethylornithine (DFMO) in combination with Dinutuximab/GM-CSF/IL-2 and Isotretinoin versus those receiving Dinutuximab/GM-CSF/IL-2 and isotretinoin alone.
Number of subjects required to go off therapy due to treatment-related adverse events as assessed by CTCAE v4.0. 1 year At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:
1. Subject has a targeted agent identified
2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
3. Subject is not removed from study due to targeted agent drug related toxicity.
Trial Locations
- Locations (26)
Penn State Milton S. Hershey Medical Center and Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
St. Lukes
🇺🇸Boise, Idaho, United States
Connecticut Children's Hospital
🇺🇸Hartford, Connecticut, United States
UCSF Benioff Children's Hospital Oakland-
🇺🇸Oakland, California, United States
Augusta University Health
🇺🇸Augusta, Georgia, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
UHC Sainte-Justine
🇨🇦Montréal, Quebec, Canada
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Children's Medical Center
🇺🇸Dallas, Texas, United States
Advocate Children's Medical Group
🇺🇸Chicago, Illinois, United States
Nicklaus Children's Miami
🇺🇸Miami, Florida, United States
Rady Children's Hospital
🇺🇸San Diego, California, United States
Children's Hospital and Clinics of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Alabama, Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Randall Children's Hospital
🇺🇸Portland, Oregon, United States
St. Joseph's Children's Hospital
🇺🇸Tampa, Florida, United States
Helen DeVos Children's Hospital
🇺🇸Grand Rapids, Michigan, United States
Cardinal Glennon Children's Medical Center
🇺🇸Saint Louis, Missouri, United States
Levine Children's Hospital
🇺🇸Charlotte, North Carolina, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Arnold Palmer Hospital for Children
🇺🇸Orlando, Florida, United States
University of Louisville
🇺🇸Louisville, Kentucky, United States
Children's Mercy Hospitals and Clinics
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
Dell Children's Blood and Cancer Center
🇺🇸Austin, Texas, United States