A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis
Status:
Completed
Trial end date:
2021-06-22
Target enrollment:
Participant gender:
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.
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.