NeuroblastomaPhase 1Aflac ST1001NCT01319838
Aflac ST1001 Prolonged Isotretinoin
A Phase 1 study testing Isotretinoin in people with Neuroblastoma, run by Emory University at 1 site in United States.
Trial summary
Neuroblastoma is a cancer of the nervous system and accounts for 15% of cancer related deaths in children. With the advancement of treatment therapies, the long term survival rate has progressed to approximately 50%. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Isotretinoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Dec 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- <=30 years of age
- histologic verification of neuroblastoma
- no active measurable disease on CT/MRI
- ultra high risk status by having mixed response, no response or stable disease following initial treatment or by having recurrent neuroblastoma
- Karnofsky >=50% for patients >16 years and Lansky >=50% for patients <=16 years
- patients must have completed high risk therapy
- organ function as defined in protocol
Who cannot join
- patients with active measurable disease
- patients who are pregnant or breast-feeding
- concomitant medications stopped as indicated in protocol
- patients with uncontrolled infection
- patients with history of depression or psychotic disorder requiring medication
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
Official title: Prolonged Isotretinoin Therapy in Patients With High Risk Neuroblastoma
Neuroblastoma is a cancer of the nervous system and accounts for 15% of cancer related deaths in children. With the advancement of treatment therapies, the long term survival rate has progressed to approximately 50%. The therapy used for treatment, however, is very toxic and associated with serious long-term side effects. Treatment for neuroblastoma typically includes chemotherapy, surgery, stem cell transplantation, radiation therapy, and immunotherapy. At the end of this treatment, children with neuroblastoma commonly take the drug isotretinoin for 6 months. Isotretinoin maintains the response to previous treatments and helps turn the remaining cancer cells into normal nerve cells.
Most patients often respond to this treatment at first but are at a high-risk for the cancer coming back. The majority of the children who relapse after treatment or develop recurrent disease do so in the first two years following the completion of therapy and there are no current treatments to cure those who relapse. This study will explore whether or not extending the therapy with isotretinoin from 6 months to 24 months will help prevent the cancer from coming back without causing severe side effects.
Read the detailed description
Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 15% of all pediatric cancer related deaths. The majority of patients present with high-risk disease that is widely metastatic and aggressive. Historically, less than 30% of these patients achieved long-term disease-free survival and the majority of relapses occurred within the first 24 months following treatment. Survival rates have modestly improved with the addition of high-dose chemotherapy and stem cell rescue, radiotherapy, surgery and biologic therapy, yet 50% of patients still succumb to their disease. Current treatment of neuroblastoma also carries significant acute toxicities and those patients that are cured suffer significant long-term treatment-related morbidities. Therefore, children with high-risk neuroblastoma are in need of novel therapeutic strategies that will improve cure rates without adding to acute and long-term toxicities.
Retinoids, derivatives of vitamin A, have been repeatedly shown to arrest cell growth of neuroblastoma cells in vitro by causing differentiation. Clinical trials in relapsed neuroblastoma patients with bulky tumors failed to show significant responses to retinoid therapy. Subsequently, however, a sentinel randomized clinical trial demonstrated that isotretinoin(13-cis-retinoic acid), when given to patients with minimal residual disease following consolidation chemotherapy, independently improved the overall survival of patients with high-risk neuroblastoma. The treatment regimen included isotretinoin for 2 weeks followed by a 2 week rest period for 6 treatment cycles. The treatment was very well tolerated with minimal side effects. The duration of treatment, 6 months, was arbitrarily chosen and currently many institutions implement prolonged retinoic acid treatment in patients with relapsed high-risk disease, yet no formal study has been done to statistically show improved survival with prolonged biotherapy.
To improve the progression-free survival in patients with high-risk neuroblastoma this trial will prolong therapy with isotretinoin to 24 months, the time window in which most relapses occur. The treatment is anticipated to be well tolerated with no increase in adverse side effects based on the benign side effect profile of patients who have received the typical 6 month treatment course. The trial will consist of a single arm of 20 high-risk neuroblastoma patients who will receive a total of 24 cycles of isotretinoin (2 weeks on treatment followed by 2 weeks of rest) compared to the historical and current COG study treatment of 6 cycles. Patients will be accrued over a 3-year period.
The toxicity and tolerability of a prolonged course of isotretinoin biologic therapy will be closely monitored with a focus on neuropsychologic and bone toxicities, and isotretinoin drug levels will be measured to determine if there is a correlation between levels and anti-tumor efficacy or toxicities. This will provide complementary data to support future national cooperative group trials.
- Conditions
- Neuroblastoma
- Being tested
- Isotretinoin
- Keywords
- neuroblastoma, isotretinoin
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsotretinoinDrug
>12 kg: 160 mg/m2/day, given PO, divided BID <=12 kg: 5.33 mg/kg/day, given PO, dividied BID doses given days 1-14 of 28 day cycle for 24 consecutive cycles
| Study group | Role | What they receive |
|---|---|---|
| isotretinoin prolongation | Experimental | Prolonged treatment with isotretinoin, extending standard 6 month duration to 2 years Receives: Drug: Isotretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
To determine the progression free survival in patients with high risk neuroblastoma who receive a prolonged course of biologic therapy with isotretinoin
Measured: 5 years after treatment completed
Isotretinoin toxicity
To determine the toxicity and tolerability of a prolonged course of isotretinoin biologic therapy
Measured: 5 years after treatment completed
Secondary outcomes (3)
Bone growth effect
To observe any effects on bone growth and metabolism in patients receiving a prolonged course of isotretinoin biologic therapy
Measured: 5 years after treatment completed
Isotretinoin pharmacokinetic profile
To determine changes in time of the pharmacokinetic profile of a prolonged course of isotretinoin biologic immunotherapy
Measured: 1 year after treatment completed
Neurologic or psychologic sequelae
To observe the incidence of neurologic or psychologic sequelae resulting from a prolonged course of isotretinoin biologic therapy
Measured: 1 year after treatment completed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2011 (estimated)
- Study startMar 2011
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: no patient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Responsible party
- Principal investigator, Muna Qayed, Emory University
- Investigators
- Howard Katzenstein, MD, Principal investigator, Children's Healthcare of Atlanta/Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319838
- Sponsor's protocol ID
- IRB00047148
- Other IDs
- Aflac ST1001
- Acronym
- Aflac ST1001
- Status last verified
- Dec 2013
- First submitted
- 18 Mar 2011
- Last updated
- 10 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prolonged Isotretinoin Therapy in Patients With High Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT01319838
- Acronym / sponsor ID
- Aflac ST1001 / IRB00047148
- Conditions
- Neuroblastoma
- Keywords
- neuroblastoma, isotretinoin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no patient enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Study start
- Mar 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 22 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neuroblastoma is a cancer of the nervous system and accounts for 15% of cancer related deaths in children. With the advancement of treatment therapies, the long term survival rate has progressed to approximately 50%. The therapy used for treatment, however, is very toxic and associated with serious long-term side effects. Treatment for neuroblastoma typically includes chemotherapy, surgery, stem cell transplantation, radiation therapy, and immunotherapy. At the end of this treatment, children with neuroblastoma commonly take the drug isotretinoin for 6 months. Isotretinoin maintains the response to previous treatments and helps turn the remaining cancer cells into normal nerve cells.
Most patients often respond to this treatment at first but are at a high-risk for the cancer coming back. The majority of the children who relapse after treatment or develop recurrent disease do so in the first two years following the completion of therapy and there are no current treatments to cure those who relapse. This study will explore whether or not extending the therapy with isotretinoin from 6 months to 24 months will help prevent the cancer from coming back without causing severe side effects.
Detailed description
Neuroblastoma is the most common extracranial solid tumor of childhood and accounts for 15% of all pediatric cancer related deaths. The majority of patients present with high-risk disease that is widely metastatic and aggressive. Historically, less than 30% of these patients achieved long-term disease-free survival and the majority of relapses occurred within the first 24 months following treatment. Survival rates have modestly improved with the addition of high-dose chemotherapy and stem cell rescue, radiotherapy, surgery and biologic therapy, yet 50% of patients still succumb to their disease. Current treatment of neuroblastoma also carries significant acute toxicities and those patients that are cured suffer significant long-term treatment-related morbidities. Therefore, children with high-risk neuroblastoma are in need of novel therapeutic strategies that will improve cure rates without adding to acute and long-term toxicities.
Retinoids, derivatives of vitamin A, have been repeatedly shown to arrest cell growth of neuroblastoma cells in vitro by causing differentiation. Clinical trials in relapsed neuroblastoma patients with bulky tumors failed to show significant responses to retinoid therapy. Subsequently, however, a sentinel randomized clinical trial demonstrated that isotretinoin(13-cis-retinoic acid), when given to patients with minimal residual disease following consolidation chemotherapy, independently improved the overall survival of patients with high-risk neuroblastoma. The treatment regimen included isotretinoin for 2 weeks followed by a 2 week rest period for 6 treatment cycles. The treatment was very well tolerated with minimal side effects. The duration of treatment, 6 months, was arbitrarily chosen and currently many institutions implement prolonged retinoic acid treatment in patients with relapsed high-risk disease, yet no formal study has been done to statistically show improved survival with prolonged biotherapy.
To improve the progression-free survival in patients with high-risk neuroblastoma this trial will prolong therapy with isotretinoin to 24 months, the time window in which most relapses occur. The treatment is anticipated to be well tolerated with no increase in adverse side effects based on the benign side effect profile of patients who have received the typical 6 month treatment course. The trial will consist of a single arm of 20 high-risk neuroblastoma patients who will receive a total of 24 cycles of isotretinoin (2 weeks on treatment followed by 2 weeks of rest) compared to the historical and current COG study treatment of 6 cycles. Patients will be accrued over a 3-year period.
The toxicity and tolerability of a prolonged course of isotretinoin biologic therapy will be closely monitored with a focus on neuropsychologic and bone toxicities, and isotretinoin drug levels will be measured to determine if there is a correlation between levels and anti-tumor efficacy or toxicities. This will provide complementary data to support future national cooperative group trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| isotretinoin prolongation | Experimental | Drug: IsotretinoinProlonged treatment with isotretinoin, extending standard 6 month duration to 2 years |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- <=30 years of age
- histologic verification of neuroblastoma
- no active measurable disease on CT/MRI
- ultra high risk status by having mixed response, no response or stable disease following initial treatment or by having recurrent neuroblastoma
- Karnofsky >=50% for patients >16 years and Lansky >=50% for patients <=16 years
Key exclusion criteria (5 listed)
- patients with active measurable disease
- patients who are pregnant or breast-feeding
- concomitant medications stopped as indicated in protocol
- patients with uncontrolled infection
- patients with history of depression or psychotic disorder requiring medication
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 |
|---|---|---|
| Isotretinoin>12 kg: 160 mg/m2/day, given PO, divided BID <=12 kg: 5.33 mg/kg/day, given PO, dividied BID doses given days 1-14 of 28 day cycle for 24 consecutive cycles | Drug | isotretinoin prolongation |
Primary outcome
Progression free survival
Time frame: 5 years after treatment completed
To determine the progression free survival in patients with high risk neuroblastoma who receive a prolonged course of biologic therapy with isotretinoin
Isotretinoin toxicity
Time frame: 5 years after treatment completed
To determine the toxicity and tolerability of a prolonged course of isotretinoin biologic therapy
3 secondary outcomes
Bone growth effect
Time frame: 5 years after treatment completed
Isotretinoin pharmacokinetic profile
Time frame: 1 year after treatment completed
Neurologic or psychologic sequelae
Time frame: 1 year after treatment completed
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2013.
- clinical trials 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.
Howard Katzenstein, MD principal investigator
Children's Healthcare of Atlanta/Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Isotretinoin in people with Neuroblastoma, run by Emory University at 1 site 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 7 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: withdrawn, as of the sponsor's last update on 10 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Progression free survival (time frame: 5 years after treatment completed). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Dec 2013.