Clinical Trials /

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

NCT02574728

Description:

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.

Related Conditions:
  • Malignant Brain Neoplasm
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Sirolimus in Combination With Metronomic Chemotherapy in Children With Recurrent and/or Refractory Solid and CNS Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: IRB00082488
  • NCT ID: NCT02574728

Conditions

  • Cancer

Interventions

DrugSynonymsArms
SirolimusRapamune, rapamycinOral sirolimus, celecoxib, etoposide, and cyclophosphamide
CelecoxibOral sirolimus, celecoxib, etoposide, and cyclophosphamide
EtoposideEtopophos, ToposarOral sirolimus, celecoxib, etoposide, and cyclophosphamide
CyclophosphamideCytoxanOral sirolimus, celecoxib, etoposide, and cyclophosphamide

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Oral sirolimus, celecoxib, etoposide, and cyclophosphamideExperimentalParticipants in this group will receive oral sirolimus and celecoxib in addition to cycles of oral etoposide and cyclophosphamide for up to two years.
  • Sirolimus
  • Celecoxib
  • Etoposide
  • Cyclophosphamide

Eligibility 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
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in radiographic response to treatment for solid tumors
Time Frame:Baseline, End of Treatment (Up to 2 years)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Number of adverse events
Time Frame:Baseline, End of Treatment (Up to 2 years)
Safety Issue:
Description:The adverse events associated with sirolimus in combination with metronomic chemotherapy administered on this schedule will be defined and evaluated throughout the treatment period.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

Trial Keywords

  • Pediatrics
  • Brain Tumors
  • Neuroblastoma
  • Osteosarcoma
  • Ewing's Sarcoma
  • Rhabdomyosarcoma
  • Wilms Tumors
  • Soft Tissue Sarcomas

Last Updated

August 16, 2019