NeuroblastomaPhase 1NCT01059071
Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
A Phase 1 study testing DFMO and Etoposide in people with Neuroblastoma, run by Giselle Sholler at 7 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- DFMO and Etoposide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 7 sitesUnited States
- Study dates
- Feb 2010to May 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
UVM/FAHC
Burlington, Vermont, 05401
Levine Children's Hospital
Charlotte, North Carolina, 28204
Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Connecticut Children's Hospital
Hartford, Connecticut, 06106
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
Children's Hospital of Orange County
Orange, California, 92868
Arnold Palmer Hospital for Children- MD Anderson
Orlando, Florida, 32806
About this study
Official title: 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.
Read more
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).
- Conditions
- Neuroblastoma
- Being tested
- DFMO, Etoposide
- Keywords
- Refractory Neuroblastoma, Relapsed neuroblastoma
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DFMODrug
Also called Difluoromethylornithine
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
EtoposideDrug
Also called Eposin, Etopophos, Vepesid, VP-16
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.
| Study group | Role | What they receive |
|---|---|---|
| DFMO and Etoposide | Experimental | Not described Receives: Drug: DFMO; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
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
Measured: length of study plus 30 days
Secondary outcomes (5)
Progression Free Survival (PFS)
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
Measured: 2 years
Number of Patients With an Overall Response Rate (ORR) of PR or CR
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.
Measured: 1 year
Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
Measured: 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.
Measured: 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.
Measured: Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2010 (estimated)
- Study startFeb 2010
- Primary completionOct 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Giselle Sholler
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Prevention Pharmaceuticals, Inc., University of Arizona, University of Hawaii
- Responsible party
- Sponsor-investigator, Giselle Sholler, Milton S. Hershey Medical Center
- Investigators
- Giselle Sholler, MD, Study chair, Beat Childhood Cancer at Atrium Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01059071
- Sponsor's protocol ID
- NMTRC 002
- Status last verified
- Aug 2024
- First submitted
- 26 Jan 2010
- Last updated
- 6 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One. 2015 May 27;10(5):e0127246. doi: 10.1371/journal.pone.0127246. eCollection 2015.
PubMed 26018967
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide
- ClinicalTrials.gov ID
- NCT01059071
- Acronym / sponsor ID
- NMTRC 002
- Conditions
- Neuroblastoma
- Keywords
- Refractory Neuroblastoma, Relapsed neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Giselle ShollerUniversity, hospital or other
- Collaborators
- Cancer Prevention Pharmaceuticals, Inc., University of Arizona, University of Hawaii
- Study start
- Feb 2010
- Primary completion
- Oct 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 29 Jan 2010 (estimated)
- Results
- Posted 20 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DFMO and Etoposide | Experimental | Drug: DFMO, Drug: Etoposide |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DFMOAlso: DifluoromethylornithineEscalating 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 | Drug | DFMO and Etoposide |
| EtoposideAlso: Eposin, Etopophos, Vepesid, VP-16Starting 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. | Drug | DFMO and Etoposide |
Primary outcome
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
5 secondary outcomes
Progression Free Survival (PFS)
Time frame: 2 years
Number of Patients With an Overall Response Rate (ORR) of PR or CR
Time frame: 1 year
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26018967Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One. 2015 May 27;10(5):e0127246. doi: 10.1371/journal.pone.0127246. eCollection 2015.
- Beat Childhood Cancer Consortium websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giselle Sholler, MD study chair
Beat Childhood Cancer at Atrium Health
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DFMO and Etoposide in people with Neuroblastoma, run by Giselle Sholler at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events as a Measure of Safety and Tolerability (time frame: length of study plus 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01059071, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.