Clinical Trial: Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Sirolimus in Combination With Metronomic Therapy in Children With Recurrent and Refractory Solid Tumors: A Phase I Study

Brief Summary:

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.


Detailed Summary: 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.
Sponsor: Emory University

Current Primary Outcome: Maximum tolerated dose (MTD) [ Time Frame: 2 years after treatment starts ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • define and describe toxicities of sirolimus [ Time Frame: 2 years post treatment ]
    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 ]
    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 ]
    To evaluate the correlation of p70S6 kinase activity inhibition with tumor response.
  • evaluate risk of infection [ Time Frame: 2 years post treatment ]
    To evaluate the effect of this combination therapy on lymphocyte subsets and memory T-cells, and to correlate that with risk of infection.


Original Secondary Outcome: Same as current

Information By: Emory University

Dates:
Date Received: April 6, 2011
Date Started: April 2011
Date Completion: April 2021
Last Updated: April 18, 2017
Last Verified: April 2017