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Aflac ST1001 Prolonged Isotretinoin (Aflac ST1001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01319838
Recruitment Status : Withdrawn (no patient enrollment)
First Posted : March 22, 2011
Last Update Posted : December 10, 2013
Children's Healthcare of Atlanta
Information provided by (Responsible Party):
Muna Qayed, Emory University

Tracking Information
First Submitted Date  ICMJE March 18, 2011
First Posted Date  ICMJE March 22, 2011
Last Update Posted Date December 10, 2013
Study Start Date  ICMJE March 2011
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 18, 2011)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01319838 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2011)
  • Bone growth effect [ Time Frame: 5 years after treatment completed ]
    To observe any effects on bone growth and metabolism in patients receiving a prolonged course of isotretinoin biologic therapy
  • Isotretinoin pharmacokinetic profile [ Time Frame: 1 year after treatment completed ]
    To determine changes in time of the pharmacokinetic profile of a prolonged course of isotretinoin biologic immunotherapy
  • Neurologic or psychologic sequelae [ Time Frame: 1 year after treatment completed ]
    To observe the incidence of neurologic or psychologic sequelae resulting from a prolonged course of isotretinoin biologic therapy
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Aflac ST1001 Prolonged Isotretinoin
Official Title  ICMJE Prolonged Isotretinoin Therapy in Patients With High Risk Neuroblastoma
Brief 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%. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroblastoma
Intervention  ICMJE Drug: 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
Study Arms  ICMJE Experimental: isotretinoin prolongation
Prolonged treatment with isotretinoin, extending standard 6 month duration to 2 years
Intervention: Drug: Isotretinoin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: December 9, 2013)
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2011)
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • <=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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01319838
Other Study ID Numbers  ICMJE IRB00047148
Aflac ST1001 ( Other Identifier: Other )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Muna Qayed, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Children's Healthcare of Atlanta
Investigators  ICMJE
Principal Investigator: Howard Katzenstein, MD Children's Healthcare of Atlanta/Emory University
PRS Account Emory University
Verification Date December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP