NCT01684449

Gemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma

Phase 1/2, Randomized, Multicenter, Prospective Study of Gemcitabine and Rapamycin (Sirolimus) Combination Versus Gemcitabine Only to Treat Advanced Soft Tissue Sarcoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Grupo Espanol de Investigacion en Sarcomas · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The soft tissue sarcomas (STS) constitute an infrequent group of malignant neoplasms of mesenchymal origin. In Spain, the approximate incidence is of 2 new cases per 100.000 inhabitants every year. In patients with metastatic STS, the average survival is very short, approximately 12 months. The systemic treatment of the metastatic disease has had a very limited development, with few satisfactory results. This facts reflect the urgent need to identify new active agents for treatment of these patients. The molecular pathway of the serine/threonine kinase mammalian target of rapamycin (mTOR) plays a central role in the regulation of the proteins translation, cellular growth and metabolism (Meric-Bernstam F et al. 2009). Currently, the mTOR pathway is considered a relevant target for the development of anti-cancer drugs, as rapamycin. Preliminary results of some clinical trials suggest that mTOR inhibitors could have some clinical activity for different types of sarcoma, including STS (Chawla et al Proc.ASCO 2006; Schuetze et al. Proc.ASCO 2006). Gemcitabine is a chemotherapy antimetabolite agent with a broad antitumoral spectrum. The activity of this drug to treat resistant sarcomas and its reduced toxicity make from gemcitabine an adequate candidate for its study in combination with new drugs addressed to molecular targets in the STS treatment. Pre-clinical studies suggest that mTOR inhibitors could have a potential synergistic or additive effect with some chemotherapy agents. The combination of rapamycin and gemcitabine seems to be a reasonable strategy to explore for the STS treatment.

Conditions

• Advanced Soft Tissue Sarcoma

Interventions

Type	Name	Description
DRUG	Gemcitabine + Rapamycin	Gemcitabine + rapamycin at recommended dose of Phase 1. Recommended dose is defined as, the dose one level below of the (MTD). Being MTD, the dose of the cohort in which a maximum of one patient of 6 has presented dose-limiting toxicity (DLT). Every three weeks until disease progression or unacceptable toxicity. The treatment will last for 6 cycles if there is not progression or intolerable toxicity. Additionally, there will be a pharmacokinetic study in a minimum of 9 patients treated with the drug combination.

Timeline

• Start date: 2010-01-01
• Primary completion: 2013-05-01
• Completion: 2013-12-01
• First posted: 2012-09-13
• Last updated: 2015-10-27

Locations

9 sites across 1 country: Spain