NCT04469530 · Emory University
Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors
(AflacST1903)
What this study is about
The primary objective of this study is to improve the 2-year time without the disease getting worse in children with high-risk solid tumors who are administered a maintenance regimen with continuous sirolimus administered on a backbone of metronomic chemotherapy following the completion of "standard" therapy, as compared to high-risk solid tumor patients treated with observation alone following completion of "standard" therapy.
View original scientific description
The primary objective of this study is to improve the 2-year progression-free survival in children with high-risk solid tumors who are administered a maintenance regimen with continuous sirolimus administered on a backbone of metronomic chemotherapy following the completion of "standard" therapy, as compared to high-risk solid tumor patients treated with observation alone following completion of "standard" therapy.
Interventions
DRUG
Sirolimus
Sirolimus is given at a dose of 2 mg/m2 once daily. The amber oral dose syringe should be used to withdraw the prescribed amount of sirolimus oral solution from the bottle. The solution can be drunk or administered at once to assure delivery of all of the medication. It is safe for administration through a nasogastric or G-tube. For tablets, the tablet should not be crushed, split, or otherwise altered. As with the liquid dosing form, the tablets should be given within two hours each day and should be at consistent intervals with regard to meals.
DRUG
Cyclophosphamide
A synthetic antineoplastic drug chemically related to the nitrogen mustards. The drug is administered orally daily, in the formulation appropriate for age. The solution should be diluted in 20-30 ml of appropriate liquid before administration through nasogastric (NG) tube or gastrostomy (G) tube, with adequate flushing after administration to prevent obstruction of the feeding tube.
DRUG
Etoposide
A semisynthetic derivative of podophyllotoxin which functions as mitotic inhibitor but does not interfere with microtubular assembly. The drug is administered orally daily, in the formulation appropriate for age.
DRUG
Celecoxib
The drug is administered orally daily, in the formulation appropriate for age.The solution is safe for administration through a nasogastric or G-tube.
Primary outcome measures
Two-year progression-free survival in patients with high-risk solid tumors
Time frame: up to 2 years
Two-year progression-free survival in patients with high-risk solid tumors who complete a 12- month course of maintenance chemotherapy with daily sirolimus and twice daily celecoxib on a backbone of low-dose oral metronomic chemotherapy following completion of "standard" therapy as compared to a historical cohort of matched patients treated with observation only following completion of "standard" therapy.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Subjects must be ≥ 12 months and ≤ 30 years of age at the time of study enrollment.
- Subjects must have one of the following high-risk malignant pediatric extracranial solid tumors and be in complete remission or have minimal abnormalities on imaging studies after completion of upfront therapy administered with curative intent (cohort 1) or after completion of initial relapse regimen.
- Prospective Cohort 1:
- Metastatic/unresectable osteosarcoma, metastatic Ewing or Ewing-like sarcoma, high-risk rhabdomyosarcoma, metastatic non-rhabdomyosarcoma soft tissue sarcoma, desmoplastic small round cell tumor (DSRCT), malignant rhabdoid tumor.
- Additional high-risk solid tumors at the request of the treating physician after approval by the study chair.
- Primary central nervous system (CNS) tumors and lymphomas are not eligible.
- Prospective Cohort 2: Recurrent extracranial solid tumor (any histology) in second complete remission following completion of initial relapse regimen.
- Subjects must have had histologic verification of malignancy at original diagnosis or relapse.
- Subjects must be in complete remission or with minimal radiological abnormalities. Baseline imaging should be the end of therapy imaging obtained at the completion of "standard" upfront therapy (cohort 1) or at the completion of initial relapse regimen (cohort 2).
- Karnofsky ≥ 50% for subjects \> 16 years of age and Lansky ≥ 50% for subjects ≤ 16 years of age.
- Subjects must have fully recovered from the acute non-hematologic toxic effects of all prior anti-cancer therapy and meet hematologic count parameters. Chronic non-hematologic toxic effects of prior anti-cancer therapy (ie peripheral neuropathy) must be improved to at least grade 2 and be stable or improving on current management.
- Adequate bone marrow function defined as absolute neutrophil count (ANC) ≥ 750/μL and platelet count ≥ 50,000/μL (transfusion independent, defined as not receiving platelet transfusions within 7 days prior to enrollment).
- Adequate renal function defined as creatinine clearance or radioisotope glomerular filtration rate (GFR) 70ml/min/1.73 m2 or serum creatinine based on age/gender values derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC).
- Adequate liver function defined as: total bilirubin ≤ 2x upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 225 U/L (5x the ULN).
- Serum triglyceride level ≤300 mg/dL and serum cholesterol ≤ 300 mg/dL.
- Random blood glucose ≤ 1.5x ULN for age.
- Adequate pulmonary function defined as normal pulmonary function tests (PFTs), if there is a clinical indication for determination (dyspnea at rest, known requirement for supplemental oxygen). For subjects who do not have respiratory symptoms (no dyspnea at rest, O2 sat ≥ 93% on room air), PFTs are not required.
Exclusion criteria
- Pregnant or breast-feeding women will not be entered on this study as there may be fetal risks or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during treatment and for 3 months after stopping treatment.
- Concomitant Medication
- Subjects receiving corticosteroids must be on a stable or decreasing dose of corticosteroid for the prior 7 days.
- Subjects who are currently receiving enzyme inducing anticonvulsants are not eligible.
- Subjects must not be receiving potent CYP3A4 inducers or inhibitors.
- Subjects who are currently receiving another investigational drug are not eligible.
- Subjects who are currently receiving any other anti-cancer agents are not eligible.
- Subjects who have an uncontrolled infection are not eligible.
- Subjects enrolled on a clinical trial for upfront therapy or relapse therapy for those patients in second complete remission.
- Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
Where
- Atlanta, Georgia
- St Louis, Missouri
- Pittsburgh, Pennsylvania
- Houston, Texas
Collaborators
PeachBowl LegACy Fund
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Feb 27, 2026 · Source of record for eligibility and locations