Last updated on July 2018

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

Brief description of study

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/-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 -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/-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.

Detailed Study Description

We propose a translational research project that will directly test the hypothesis that mTOR is active in desmoid tumor in children and young adults. Activity will be assessed by clinical and histological studies following a course of pre-operative chemotherapy using sirolimus. Clinical response will be measured using validated pain assessment scales because desmoid tumor size is unlikely to change during the course of pre-operative chemotherapy in this study. Histological response will be based on quantifying the phosphorylation of following mTOR targets: thr389p-p70S6K, p-4E-BP1, and ser473p-AKT.

Clinical Study Identifier: NCT01265030

Contact Investigators or Research Sites near you

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Noah Federman, MD

UCLA Medical Center
Los Angeles, CA United States
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Aaron R Weiss, DO

Maine Medical Center
Portland, ME United States
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Michelle Manalang, MD

Children's Mercy Hospital
Kansas City, MO United States
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Douglas Hawkins

Seattle Children's Hospital
Seattle, WA United States
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Sun H Choo, MD

Rady Children's Hospital
San Diego, CA United States
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Giselle Moore-Higgs, PhD

University of Florida College of Medicine
Gainesville, FL United States
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Brenda Weigel, MD

University of Minnesota
Minneapolis, MN United States
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Meghen Browning, MD

Medical College of Wisconsin
Milwaukee, WI United States
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Recruitment Status: Open

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