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 : December 20, 2022
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Condition or disease | Intervention/treatment | Phase |
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Cancer | Drug: Sirolimus Drug: Celecoxib Drug: Etoposide Drug: Cyclophosphamide | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 60 participants |
Allocation: | N/A |
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 : | January 2024 |
Estimated Study Completion Date : | January 2024 |

Arm | Intervention/treatment |
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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.
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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:
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:
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 |
- 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).
- 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 |
Inclusion Criteria:
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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) - enrollment in the brain tumor stratum is closed
- 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. Measurable disease in patients with CNS involvement is defined as tumor that is measurable (≥ 10 mm) in two perpendicular diameters on MRI and visible on more than one slice. For all patients, tumors that are located in a previously irradiated area may be considered measurable if the lesion has shown tumor growth after radiation or has been biopsied and proven to have active disease.
- Participant's current disease state must be one for which there is no known curative therapy
- 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

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
Contact: Thomas Cash, MD | aflacdevtreferral@choa.org |
United States, Arizona | |
Phoenix Children's Hospital | Recruiting |
Phoenix, Arizona, United States, 85016 | |
Contact: Laura Evdokimo 602-933-5004 levdokimo@phoenixchildrens.com | |
Principal Investigator: Lindsey Hoffman, DO | |
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: Emi Caywood, MD | |
United States, Georgia | |
Children's Healthcare of Atlanta-Egleston | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Thomas Cash, MD aflacdevtreferral@choa.org | |
Principal Investigator: Thomas Cash, MD | |
Children's Healthcare of Atlanta, Scottish Rite | Recruiting |
Atlanta, Georgia, United States, 30342 | |
Contact: Thomas Cash, MD aflacdevtreferral@choa.org | |
Principal Investigator: Thomas Cash, MD | |
United States, Missouri | |
Children's Mercy Hospital | Recruiting |
Kansas City, Missouri, United States, 64108 | |
Contact: Robin E Ryan, MPH 816-302-6849 rryan@cmh.edu | |
Principal Investigator: Kevin Ginn, 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 |
Principal Investigator: | Thomas Cash, MD | Emory University |
Responsible Party: | Thomas Cash, Associate Professor, Emory University |
ClinicalTrials.gov Identifier: | NCT02574728 |
Other Study ID Numbers: |
IRB00082488 |
First Posted: | October 14, 2015 Key Record Dates |
Last Update Posted: | December 20, 2022 |
Last Verified: | December 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Pediatrics Brain Tumors Medulloblastoma Ependymoma Atypical teratoid rhabdoid tumor (ATRT) Pineoblastoma Germ cell tumors (CNS and non-CNS) Neuroblastoma Osteosarcoma |
Ewing's Sarcoma Rhabdomyosarcoma Wilms Tumors Soft Tissue Sarcomas Langerhans cell histiocytosis (LCH) Histiocytic disorders Rare pediatric solid tumors Carcinomas |
Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Neoplasms Nervous System Diseases Sirolimus Celecoxib Cyclophosphamide 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 Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents |