A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis
Desmoid-type fibromatosis (or desmoid tumor) represents an intermediate grade neoplasm with a striking predilection for locally invasive growth and recurrence following resection. It occurs in children as well as young adults. As a typically localized disease, the historical standard of care for treatment has been surgical resection, with or without ionizing radiation. In some cases where surgical resection or radiation is not feasible, chemotherapy has been used. Two clinical trials conducted in the Pediatric Oncology Group (POG) and the Children's Oncology Group (COG) evaluated the role for either low intensity or non-cytotoxic chemotherapy for children with desmoid tumor that is not amenable to standard therapy. These were largely empirical treatment strategies or based on somewhat anecdotal observations. By better understanding desmoid tumor biology, even more effective therapy targeting a particular protein that is central to the disease can be developed.
Desmoid tumor is well-known to be associated with deregulation of the Adematous Polyposis Cell/beta-catenin (APC/β-catenin pathway). This is true of familial cases associated with Gardner's Syndrome and also in sporadic desmoid tumor, nearly all of which display histological or molecular evidence of Adematous Polyposis Cell/beta-catenin (APC β-catenin) pathway activation (Alman et al., 1997; Lips et al., 2009). Several new pieces of evidence support the concept that deregulation of the mammalian target of rapamycin (mTOR) cell proliferation/survival pathway may play an important role in tumor biology when the APC/β-catenin pathway is disrupted. Sirolimus, a drug that inhibits mammalian target of rapamycin (mTOR), is currently being evaluated as an anti-cancer agent in a variety of tumor types, but it has not been previously studied in desmoid tumor.
The investigators are conducting this pilot study to begin to explore whether mTOR inhibition may be beneficial for children and young adults with desmoid tumor.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis|
- Determine if mTor pathway activation decreases in patients with surgically-resectable desmoid tumor removed following pre-operative treatment with sirolimus [ Time Frame: 6 months after the last subject has been enrolled ] [ Designated as safety issue: No ]To determine whether mTor pathway activation decreases in patients with surgically-resectable desmoid tumor that is removed following pre-operative treatment with sirolimus
- Assess whether sirolimus improves pain [ Time Frame: 6 months after the last subject has been enrolled ] [ Designated as safety issue: No ]To assess whether sirolimus improves desmoid tumor-associated pain.
- Explore whether pre-operative sirolimus decreases tumor recurrence following resection of high-risk tumor [ Time Frame: 6 months after last subject has been enrolled ] [ Designated as safety issue: No ]To begin to explore whether pre-operative sirolimus decreases tumor recurrence following surgical removal of desmoid tumor felt to be at high-risk for recurrence because of size and/or anatomical site.
- Assess safety and tolerability of pre-operative sirolimus in patients with desmoid [ Time Frame: 6 months after last subject is enrolled ] [ Designated as safety issue: Yes ]To assess the safety and tolerability of pre-operative sirolimus in patients with desmoid tumor.
|Study Start Date:||December 2010|
|Study Completion Date:||November 2011|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Other Name: Rapamune®, Rapamycin
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, New Jersey|
|University of Medicine and Dentistry of New Jersey/Robert Wood Johnson University Hospital|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator:||Stephen X Skapek, MD||University of Chicago|