This trial is active, not recruiting.

Conditions ewing's sarcoma, osteosarcoma, astrocytoma, atypical teratoid/rhabdoid tumor, ependymoma, germ cell tumor, glioma, medulloblastoma, rhabdoid tumor, retinoblastoma, clear cell sarcoma, renal cell carcinoma, wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma
Treatment sirolimus
Phase phase 1
Targets mTOR, FKBP-12
Sponsor Emory University
Collaborator Children's Healthcare of Atlanta
Start date April 2011
End date August 2014
Trial size 24 participants
Trial identifier NCT01331135, Aflac ST0901 CHOANOME, IRB00047016


The best treatment for recurrent cancers or those that do not respond to therapies is not known. Typically, patients with these cancers receive a combination of cancer drugs (chemotherapy), surgery, or radiation therapy. These treatments can prolong their life but may not offer a long-term cure.

This study proposes using a drug called Sirolimus in combination with common chemotherapy drugs to treat patients with recurrent and refractory solid tumors. Sirolimus has been found to inhibit cell growth and to have anti-tumor activity in pediatric solid tumors in previous studies and, therefore, has the potential to increase the effectiveness of the chemotherapy drugs when given together.

This study wil investigate the highest dose of Sirolimus that can be given orally with other oral chemotherapy drugs. Cohorts of 2 subjects will be started at the minimum dose. The dose will be increased in the next 2 subjects as long as there were no major reactions in the previous groups. This study will also seek to learn more about the side effects of sirolimus when used in this combination and what effects the drug has on the white cells and the immune system. Successful use of this drug will impact the cancer population greatly by providing an increased chance of survival to those with resistant or recurrent cancers.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Dose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2.
sirolimus rapamune
daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2.

Primary Outcomes

Maximum tolerated dose (MTD)
time frame: 2 years after treatment starts

Secondary Outcomes

define and describe toxicities of sirolimus
time frame: 2 years post treatment
anti-tumor activity of sirolimus
time frame: 2 years post treatment
evaluate correlation of p70S6 kinase activity
time frame: 2 years post treatment
evaluate risk of infection
time frame: 2 years post treatment

Eligibility Criteria

Male or female participants up to 30 years old.

Inclusion Criteria: - must be <=30 years of age at time of study enrollment - histologic verification of malignancy at original diagnosis or relapsis except in patients with intrinsic brain stem tumors, optic pathway gliomas or patients wtih pineal tumors and evaluations of serum or CSF alpha-fetoprotein or beta-HCG - measurable or evaluable disease - disease state must be one for which there is no known curative therapy - Performance level >=50% - Patients must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy or radiotherapy - no evidence of acute graft vs. host disease and >=3 months since transplant - organ function as defined in eligibility section of protocol Exclusion Criteria: - patients cannot be pregnant or breast-feeding - patients must agree to use of an effective contraceptive method - no growth factors that support platelet or white cell number or function for at least 7 days prior to enrollment - patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible - patients receiving any other investigational drugs - patients receiving any other anti-cancer drugs - patients who have an uncontrolled infection

Additional Information

Official title Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study
Principal investigator Muna Qayed, MD
Description Sirolimus, is a potent immunosuppressive drug that is approved for use in prevention against allograft rejection following solid organ transplant. It has anti-tumor effects mainly by blocking signals which drive cells from G1 to S phase during cell cycle through inhibition of mTOR, thus inhibiting cell growth. Sirolimus, as well as other mTOR inhibitors, has shown anti-tumor activity in pediatric solid tumor xenografts. Children with relapsed and/or refractory solid tumors are in need of novel therapeutic approaches. One option for these patients is the use of prolonged exposure to low dose antiangiogenic chemotherapy, with agents such as etoposide and cyclophosphamide. In this phase I trial the feasibility and optimal dosing for daily sirolimus, in combination with daily celecoxib, and low dose etoposide alternating with cyclophosphamide, will be determined in children with relapsed and refractory solid tumors. p70S6 kinase inhibition will be used as a surrogate for mTOR inhibition. The potential immunosuppressive effect of sirolimus administered on this schedule will be assessed by serial lymphocyte subsets and assessment of memory T cell number.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Emory University.