A Maintenance Protocol of Sirolimus in Combination With Metronomic Chemotherapy in Children With High-Risk Solid Tumors
Emory University
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.
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…
Eligibility
- Age range
- 1–30 years
- Sex
- All
- Healthy volunteers
- No
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 sarc…
Interventions
- DrugSirolimus
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.
- DrugCyclophosphamide
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.
- DrugEtoposide
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.
- DrugCelecoxib
The drug is administered orally daily, in the formulation appropriate for age.The solution is safe for administration through a nasogastric or G-tube.
Locations (5)
- Aflac Cancer & Blood Disorders CentersAtlanta, Georgia
- Children's Healthcare of AtlantaAtlanta, Georgia
- Washington University School of MedicineSt Louis, Missouri
- Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC)Pittsburgh, Pennsylvania
- Texas Children's Cancer CenterHouston, Texas