- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01059071
Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
A Phase I Trial 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 Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Orange, California, United States, 92868
- Children's Hospital of Orange County
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Connecticut
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Hartford, Connecticut, United States, 06106
- Connecticut Children's Hospital
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Florida
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Orlando, Florida, United States, 32806
- Arnold Palmer Hospital for Children- MD Anderson
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Michigan
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Grand Rapids, Michigan, United States, 49503
- Helen DeVos Children's Hospital
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Missouri
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Kansas City, Missouri, United States, 64108
- Children's Mercy Hospitals and Clinics
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Levine Children's Hospital
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Vermont
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Burlington, Vermont, United States, 05401
- UVM/FAHC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: DFMO and Etoposide
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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 Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: length of study plus 30 days
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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
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length of study plus 30 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: 2 years
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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
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2 years
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Number of Patients With an Overall Response Rate (ORR) of PR or CR
Time Frame: 1 year
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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.
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1 year
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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
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Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
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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
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Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
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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
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Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Giselle Sholler, MD, Beat Childhood Cancer at Atrium Health
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroectodermal Tumors, Primitive
- Neuroectodermal Tumors, Primitive, Peripheral
- Neuroblastoma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antiprotozoal Agents
- Antiparasitic Agents
- Trypanocidal Agents
- Ornithine Decarboxylase Inhibitors
- Etoposide
- Eflornithine
Other Study ID Numbers
- NMTRC 002
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neuroblastoma
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingStage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 Neuroblastoma | Stage 1 Neuroblastoma | Stage 2 NeuroblastomaUnited States, Canada, Australia, New Zealand
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Stage 4S Neuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand
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National Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)RecruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States, Puerto Rico, Canada, Australia, New Zealand, Netherlands, Saudi Arabia, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4 NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Stage 4S NeuroblastomaUnited States
Clinical Trials on DFMO
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Giselle ShollerBeat NB Cancer Foundation; K C Pharmaceuticals Inc.; Team Parker for LifeRecruitingNeuroblastomaUnited States, Canada
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Giselle ShollerRecruitingMedulloblastomaUnited States
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Giselle ShollerBeat NB Cancer Foundation; Team Parker for LifeRecruiting
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Thomas E. AhleringNational Cancer Institute (NCI)CompletedProstate CancerUnited States
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Giselle ShollerK C Pharmaceuticals Inc.; USWM, LLCAvailableEmbryonal Tumor With Abundant Neuropil and True Rosettes | Medulloblastoma | Neuroblastoma | Medulloepithelioma | Ependymoblastoma | Typical Teratoid Rhabdoid TumorUnited States
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Giselle ShollerBeat NB Cancer Foundation; Because of Ezra; K C Pharmaceuticals Inc.Active, not recruitingNeuroblastoma RecurrentUnited States
-
Giselle ShollerBeat NB Cancer Foundation; Because of Ezra; K C Pharmaceuticals Inc.Completed
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Orbus Therapeutics, Inc.Active, not recruitingAnaplastic Astrocytoma | Recurrent Anaplastic AstrocytomaUnited States, United Kingdom, France, Canada, Italy, Germany, Netherlands, Belgium
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Emily K. SimsJuvenile Diabetes Research Foundation; Cancer Prevention Pharmaceuticals, Inc.Recruiting