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Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors (AflacST1502)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02574728
Recruitment Status : Recruiting
First Posted : October 14, 2015
Last Update Posted : August 19, 2019
Sponsor:
Collaborators:
Cannonball Kids' Cancer Foundation
Hyundai Hope On Wheels
Information provided by (Responsible Party):
Thomas Cash, MD, Emory University

Tracking Information
First Submitted Date  ICMJE October 2, 2015
First Posted Date  ICMJE October 14, 2015
Last Update Posted Date August 19, 2019
Study Start Date  ICMJE June 2015
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Change in radiographic response to treatment for solid tumors [ Time Frame: Baseline, End of Treatment (Up to 2 years) ]
    Radiographic response to treatment will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) for participants with solid tumors via CT or MRI scan. A complete response (CR) is a disappearance of all target and non-target lesions. Partial response (PR) is at least a 30% decrease in the disease measurement compared to the baseline measurement. Stable disease (SD) is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD) taking as reference the smallest disease measurement since baseline. Progressive disease (PD) is at least a 20% increase in the disease measurement compared to baseline, or the appearance of one or more new lesions, or evidence of laboratory or clinical progression.
  • Change in radiographic response to treatment for central nervous system (CNS) tumors [ Time Frame: Baseline, End of Treatment (Up to 2 years) ]
    Radiographic response to treatment will be assessed for participants with CNS tumors via CT or MRI scan. Response criteria are assessed based on the lesion of the longest diameter and its longest perpendicular diameter. Development of new disease or progression in any established lesions is considered progressive disease, regardless of response in other lesions. Complete response (CR) is the the disappearance of all target lesions. Partial response (PR) is greater than or equal to 50% decrease decrease in the sum of the products of the two perpendicular diameters of all target lesions, taking into reference the baseline measurement. Stable disease (SD) is neither a sufficient decrease in the sum of the products of the two perpendicular diameters of all target lesions to qualify for PR, nor sufficient increase in a single target lesion to qualify for progressive disease (PD).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02574728 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
Number of adverse events [ Time Frame: Baseline, End of Treatment (Up to 2 years) ]
The adverse events associated with sirolimus in combination with metronomic chemotherapy administered on this schedule will be defined and evaluated throughout the treatment period.
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 Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors
Official Title  ICMJE AflacST1502: A Phase II Study of Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors
Brief Summary This study aims to determine the efficacy of daily sirolimus and celecoxib, with low dose etoposide alternating with cyclophosphamide for pediatric participants with relapsed or refractory tumors.
Detailed Description This study aims to learn if the combination of oral sirolimus once daily with celecoxib, and with oral etoposide alternating every 21 days with oral cyclophosphamide (metronomic chemotherapy) is effective in shrinking relapsed or refractory tumors in pediatric participants. In addition, this study seeks to learn the length of time this combination can keep the tumor from growing, learn more about the side effects of sirolimus when used in this combination, and to learn if the sirolimus is working by evaluating blood and tumor tissue.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: Sirolimus
    The starting dose for sirolimus is 2 mg/m2 once daily. The dose of sirolimus will be individually adjusted to achieve a target serum trough concentration in the range of 10-15 ng/ml. Sirolimus will be given by mouth every day for six weeks (every six weeks is called one cycle) for up to two years or 16 cycles.
    Other Names:
    • Rapamune
    • rapamycin
  • Drug: Celecoxib
    Celecoxib 100 mg will be given by mouth twice a day for six weeks (every six weeks is called one cycle) for up to two years or 16 cycles.
  • Drug: Etoposide
    Etoposide 50 mg/m2 (maximum dose 100 mg) will be given daily by mouth for the first 3 weeks of a 6 week cycle. Six week cycles will be repeated for up to two years or 16 cycles.
    Other Names:
    • Etopophos
    • Toposar
  • Drug: Cyclophosphamide
    Cyclophosphamide 2.5 mg/Kg (maximum dose 100 mg) will be given daily by mouth for the second 3 weeks of a 6 week cycle. Six week cycles will be repeated for up to two years or 16 cycles.
    Other Name: Cytoxan
Study Arms  ICMJE Experimental: Oral sirolimus, celecoxib, etoposide, and cyclophosphamide
Participants in this group will receive oral sirolimus and celecoxib in addition to cycles of oral etoposide and cyclophosphamide for up to two years.
Interventions:
  • Drug: Sirolimus
  • Drug: Celecoxib
  • Drug: Etoposide
  • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 12, 2015)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, and participants with tumors that carry a poor prognosis and have no known standard curative therapy

    • Brain tumors of all World Health Organization (WHO) grades, except diffuse intrinsic pontine glioma (DIPG)
    • Extracranial solid tumors including histiocytoses
  • Participants must have had a histologic verification of malignancy at original diagnosis or relapse, except in participants with optic pathway gliomas, or participants with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) or beta-human chorionic gonadotropin (beta-HCG)
  • Tissue blocks or slides must be sent
  • Participants must have radiographically measurable disease at the time of study enrollment to be eligible. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG+) evaluable disease are eligible.
  • Karnofsky performance level of greater than or equal to 50 percent for participants who are greater than 16 years of age at the time of screening
  • Lansky performance level of greater than or equal to 50 percent for participants who are less than or equal to 16 years of age at the time of screening
  • Fully recovered from acute toxic effects of all prior anti-cancer therapy
  • Adequate bone marrow function as deemed by the protocol at the time of screening
  • Adequate renal function as deemed by the study protocol at the time of screening
  • Adequate liver function as deemed by the study protocol at the time of screening
  • Serum triglyceride level ≤300 mg/dL and serum cholesterol ≤ 300 mg/dL
  • Random or fasting blood glucose within the upper normal limits for age
  • Adequate pulmonary function as deemed by the study protocol at the time of screening

Exclusion Criteria:

  • Women who are currently pregnant or breastfeeding
  • Receiving corticosteroids who have not been on a stable dose for at least 7 days
  • Currently receiving enzyme inducing anticonvulsants
  • Currently receiving receiving potent CYP3A4 (enzyme) inducers or inhibitors
  • Currently receiving another investigational drug
  • Currently receiving any other anti-cancer agents
  • The use of cannabis oil is prohibited during the first 2 cycles of this protocol. Patients must be off of cannabis oil for 3 days prior to enrollment.
  • Uncontrolled infection
  • Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kate Glasscox 404-785-0002 Katherine.GlasscoxSuggs@choa.org
Contact: Study Information AflacDevTreferral@choa.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02574728
Other Study ID Numbers  ICMJE IRB00082488
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Cash, MD, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE
  • Cannonball Kids' Cancer Foundation
  • Hyundai Hope On Wheels
Investigators  ICMJE
Principal Investigator: Thomas Cash, MD Emory University
PRS Account Emory University
Verification Date August 2019

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