NCT04469530

Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors

A Maintenance Protocol of Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Sirolimus, also known as rapamycin, is a potent immunosuppressive drug. Due to its profound immunosuppressive actions, sirolimus was initially developed and received regulatory approval for the indication of prevention of allograft rejection following solid organ transplant. Sirolimus also possesses anti-tumor activity through its anti-proliferative effect, by the inhibition of translation of key messenger ribonucleic acids (mRNAs) into proteins required for cell cycle progression from the G1 to the S phase. Palliative care with the use of antiangiogenic metronomic chemotherapy in the form of low-dose daily oral administration of etoposide and cyclophosphamide in combination with antiangiogenic agents such as celecoxib, is feasible and well-tolerated in children with refractory solid tumors Sirolimus is used orally in adults and children for the prevention of allograft rejection following solid organ transplant. The Pediatric Preclinical Testing Program (PPTP) performed testing of sirolimus as a single agent against an in vitro panel of pediatric cell lines, as well as against in vivo pediatric tumor panels. Sirolimus exhibited variable inhibition of cell line growth, ranging from 19% to 85% (median 49%). This study has three cohorts: a prospective cohort of patients with high-risk extracranial solid tumor, a prospective cohort of patients with recurrent solid tumors (any histology) in second complete remission, and a historical control cohort of patients matched on diagnosis, age, metastatic site, and date of diagnosis. The matched historical controls will be obtained from the same treating institution as the corresponding case to account for institutional differences in treatment and supportive care. The primary objective of the 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.

Conditions

• Solid Tumor

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2020-09-16
• Primary completion: 2029-02-01
• Completion: 2029-02-01
• First posted: 2020-07-14
• Last updated: 2026-02-27

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study