Clinical Trial: A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis

Brief Summary:

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 Adenomatous 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 Adenomatous 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.

To determine whether mTor pathway activation decreases in patients with surgically-resectable desmoid tumor that is removed following pre-operative treatment with sirolimus



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Assess whether sirolimus improves pain [ Time Frame: 6 months after the last subject has been enrolled ]
    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 ]
    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 ]
    To assess the safety and tolerability of pre-operative sirolimus in patients with desmoid tumor.


Original Secondary Outcome: Same as current

Information By: Maine Medical Center

Dates:
Date Received: December 6, 2010
Date Started: February 2014
Date Completion: March 2019
Last Updated: April 5, 2017
Last Verified: April 2017