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

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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

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.

Condition or disease Intervention/treatment Phase
Cancer Drug: Sirolimus Drug: Celecoxib Drug: Etoposide Drug: Cyclophosphamide Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: AflacST1502: A Phase II Study of Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors
Study Start Date : June 2015
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.

  2. 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).


Secondary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   12 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02574728


Contacts
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Contact: Kate Glasscox 404-785-0002 Katherine.GlasscoxSuggs@choa.org
Contact: Study Information AflacDevTreferral@choa.org

Locations
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United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Laura Evdokimo    602-933-5004    levdokimo@phoenixchildrens.com   
Principal Investigator: Cynthia Wetmore, MD, PhD         
United States, Delaware
Nemours/Alfred I. duPont Hospital for Children Recruiting
Wilmington, Delaware, United States, 19803
Contact: Debra Bertz, CTR, MBA    302-651-5757    debra.bertz@nemours.org   
Principal Investigator: Andrew W Walter, MD         
United States, Florida
Nemour's Children's Specialty Care Jacksonville Recruiting
Jacksonville, Florida, United States, 32207
Contact: Howard Katzenstein, MD    904-697-3985    Howard.Katzenstein@nemours.org   
Principal Investigator: Howard Katzenstein, MD         
United States, Georgia
Children's Healthcare of Atlanta-Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kate Glasscox    404-785-0002    Katherine.GlasscoxSuggs@choa.org   
Children's Healthcare of Atlanta, Scottish Rite Recruiting
Atlanta, Georgia, United States, 30342
Contact: Kate Glasscox    404-785-0002    Katherine.GlasscoxSuggs@choa.org   
Principal Investigator: Thomas Cash, MD         
United States, Missouri
Children's Mercy Hospital Recruiting
Kansas City, Missouri, United States, 64108
Contact: Amber Jenkins, MSc, CCRC    816-302-6891    amjenkins@cmh.edu   
Principal Investigator: Jaszianne Tolbert, MD         
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Cindy Fischer, CCRC    434-243-0901    CRB3Y@hscmail.mcc.virginia.edu   
Principal Investigator: William Petersen, MD         
Sponsors and Collaborators
Emory University
Cannonball Kids' Cancer Foundation
Hyundai Hope On Wheels
Investigators
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Principal Investigator: Thomas Cash, MD Emory University

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Responsible Party: Thomas Cash, MD, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT02574728     History of Changes
Other Study ID Numbers: IRB00082488
First Posted: October 14, 2015    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Thomas Cash, MD, Emory University:
Pediatrics
Brain Tumors
Neuroblastoma
Osteosarcoma
Ewing's Sarcoma
Rhabdomyosarcoma
Wilms Tumors
Soft Tissue Sarcomas
Additional relevant MeSH terms:
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Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Sirolimus
Celecoxib
Cyclophosphamide
Etoposide
Etoposide phosphate
Everolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic