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

This study is currently recruiting participants.
Verified July 2017 by Thomas Cash, MD, Emory University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02574728
First Posted: October 14, 2015
Last Update Posted: July 18, 2017
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.
Information provided by (Responsible Party):
Thomas Cash, MD, Emory University
  Purpose
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 Intervention Phase
Cancer Drug: Sirolimus Drug: Celecoxib Drug: Etoposide Drug: Cyclophosphamide Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Thomas Cash, MD, Emory University:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 60
Study Start Date: June 2015
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral sirolimus, celecoxib, etoposide, and cyclophoshphamide
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

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.
  Eligibility

Information from the National Library of Medicine

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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
  • Extracranial solid tumors including neuroblastoma
  • Bone tumors (osteosarcoma, Ewing sarcoma)
  • Rhabdomyosarcoma
  • Soft tissue sarcomas
  • Wilms tumor
  • Other rare solid tumors

Participants must have had a histologic verification of malignancy at original diagnosis or relapse, except in participants with intrinsic brain stem tumors, optic pathway gliomas, or participants with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) or beta-HCG (beta-human chorionic gonadotropin).

  • Karnofsky performance level of greater than or equal to 50 percent for participants greater than 16 years of age at the time of screening
  • Lansky performance level of greater than or equal to 50 percent for participants 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
  • 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
  • Uncontrolled infection
  • Participants who in the opinion of the investigator may not be able to comply with the safety monitoring requirements
  Contacts and Locations
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
Contact: Amy Autry-Bush 404-785-6011 amy.autry-bush@choa.org

Locations
United States, Georgia
Children's Healthcare of Atlanta-Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Amy Autry-Bush    404-785-6011    amy.autry-bush@choa.org   
Children's Healthcare of Atlanta, Scottish Rite Recruiting
Atlanta, Georgia, United States, 30342
Contact: Amy Autry-Bush    404-785-6011    amy.autry-bush@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   
Contact: Allie Bruce    816-302-6892    albruce@cmh.edu   
Principal Investigator: Keith August, MD, MS         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Thomas Cash, MD Emory University
  More Information

Responsible Party: Thomas Cash, MD, Assistant Professor, Emory University
ClinicalTrials.gov Identifier: NCT02574728     History of Changes
Other Study ID Numbers: IRB00082488
First Submitted: October 2, 2015
First Posted: October 14, 2015
Last Update Posted: July 18, 2017
Last Verified: July 2017

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:
Cyclophosphamide
Sirolimus
Everolimus
Celecoxib
Etoposide phosphate
Etoposide
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
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents