Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
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.
Atypical Teratoid/Rhabdoid Tumor
Germ Cell Tumor
Clear Cell Sarcoma
Renal Cell Carcinoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study|
- Maximum tolerated dose (MTD) [ Time Frame: 2 years after treatment starts ] [ Designated as safety issue: Yes ]estimate the maximum tolerated dose (MTD) and recommended Phase II dose of sirolimus administered orally once daily for 42 days in combination with metronomic chemotherapy in children with recurrent or refractory solid tumors.
- define and describe toxicities of sirolimus [ Time Frame: 2 years post treatment ] [ Designated as safety issue: Yes ]To define and describe the toxicities of sirolimus administered in combination with metronomic chemotherapy administered according to this schedule.
- anti-tumor activity of sirolimus [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]To assess the antitumor activity of sirolimus administered in combination with metronomic chemotherapy to children with recurrent and refractory solid tumors within the confines of a Phase I study.
- evaluate correlation of p70S6 kinase activity [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
- evaluate risk of infection [ Time Frame: 2 years post treatment ] [ Designated as safety issue: Yes ]To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||April 2021|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: sirolimus treatment
Dose escalation of sirolimus with starting dose at 1 mg/m2 and increasing to a possible 3 mg/m2.
daily administration of sirolimus in oral form starting at a dose of 1 mg/m2 and increasing to a possible 3 mg/m2.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01331135
|United States, Georgia|
|Children's Healthcare of Atlanta|
|Atlanta, Georgia, United States, 30322|
|Principal Investigator:||Muna Qayed, MD||Children's Healthcare of Atlanta|