A Pilot Study Evaluating the Use of mTor Inhibitor Sirolimus in Children and Young Adults With Desmoid-Type Fibromatosis
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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.
Condition | Intervention |
---|---|
Desmoid Tumor |
Drug: Sirolimus |
Study Type: | Interventional |
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.
Estimated Enrollment: | 15 |
Study Start Date: | December 2010 |
Estimated Study Completion Date: | December 2018 |
Estimated Primary Completion Date: | June 2016 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Experimental: Sirolimus
Preoperative sirolimus:
|
Drug: Sirolimus
Other Name: Rapamune®, Rapamycin
|
![](https://webarchive.library.unt.edu/web/20121019203807im_/http://www.clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
Ages Eligible for Study: | up to 29 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Must be less than 30 years of age at time of diagnosis
- Must have biopsy-proven desmoid tumor (or aggressive fibromatosis). For patients with recurrent disease, a biopsy is not required at the time of recurrence
- Patients known to have germ-line adenomatous polyposis coli (APC) mutations or clinical manifestations of Familial Adenomatous Polyposis(FAP)/Gardner's syndrome can be included
Patients must have surgery planned to remove the desmoid tumor and either:
- the desmoid tumor has already recurred after a prior surgery or
- the newly diagnosed disease is judged to be at high risk for recurrence due to its size (>5 centimeters) or location at an anatomic site making it unlikely to be resected with negative margins (eg. adjacent to neurovascular structures)
- There must be a commitment by the surgical team to resect the primary tumor within 1 week following the 4 weeks of sirolimus unless the clinical situation at the time of resection suggests that these interventions are not in the patient's best interest
Concomitant medication restrictions:
- Patients may not have received prior chemotherapy (excluding prior mTOR inhibitors
- Use of steroids for non-tumor indications (for example: asthma or severe allergic reaction) is permitted
- Patients must have a Karnofsky performance status of greater than or equal to 50 for patients older than 16 years of age or Lansky performance status of greater than or equal to 50 for patients less than or equal to 16 years of age.
- Patients must have a life expectancy of greater than or equal to 8 weeks.
Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea)
- Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biological agent
- Stem Cell Transplant (SCT): No evidence of active graft versus host disease. For allogeneic SCT, greater than or equal to 6 months must have elapsed.
- Patients must be able to consume oral medication in the form of tablets or solution
Patients must have normal laboratory values as defined below:
- Creatinine clearance or radioisotope Glomerular Filtration Rate ≥ 70millileters/minute/1.73 meters2 or
A serum creatinine based on age/gender as follows:
Male Female
1 month to less than 6 months 0.4 0.4 6 months to less than 1 year 0.5 0.5
- to less than 2 years 0.6 0.6
- to less than 6 years 0.8 0.8
6 to less than 10 years 1 1 10 to less than 13 years 1.2 1.2 13 to less than 16 years 1.5 1.4 greater than or equal to 16 years 1.7 1.4
Hepatic: Adequate liver function is defined as:
- Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and
- Serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 x upper limit normal (ULN) for age
Hematologic function: Adequate bone marrow function is defined as:
- Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 to the ninth/Liter
- Hemoglobin greater than or equal to 10 gram/deciliter
- Platelet count greater than or equal to 100 x 10 to the ninth/Liter
- Female patients must have a negative pregnancy test
- Female patients who are lactating must agree to stop breast-feeding
- Sexually active patients of childbearing potential must agree to use effective contraception
- Patients must be able to cooperate fully with all planned protocol therapy
- Signed informed consent MUST be obtained from patient or parent/legal guardian (if patient is less than 18 years of age). Consent must be signed prior to any study procedures and study entry
Exclusion Criteria:
- Patients with other fibroblastic lesions or other fibromatoses are NOT eligible.
Concomitant medication restrictions
- Patients may NOT have received prior mTor inhibitors
- Growth factor(s): Must not have received within 1 week of entry onto this study.
- Patients must not be known to be Human Immunodeficiency Virus positive. Testing for Human Immunodeficiency Virus is not mandatory.
- Patients must not be taking medicines known to influence sirolimus metabolism
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Contact: Stephen X Skapek, MD | 773-702-6808 | sskapek@peds.bsd.uchicago.edu |
Contact: Aaron Weiss, DO | 732-235-8862 | weissar@umdnj.edu |
United States, Illinois | |
University of Chicago | Recruiting |
Chicago, Illinois, United States, 60637 | |
Principal Investigator: Stephen X Skapek, MD | |
United States, New Jersey | |
University of Medicine and Dentistry of New Jersey/Robert Wood Johnson University Hospital | Recruiting |
New Brunswick, New Jersey, United States, 08903 | |
Contact: Aaron Weiss, DO 732-235-8862 weissar@umdnj.edu |
Principal Investigator: | Stephen X Skapek, MD | University of Chicago |
![](https://webarchive.library.unt.edu/web/20121019203807im_/http://www.clinicaltrials.gov/ct2/html/images/frame/triangle.gif)
No publications provided
Responsible Party: | Stephen X. Skapek, MD - Associate Professor, University of Chicago |
ClinicalTrials.gov Identifier: | NCT01265030 History of Changes |
Other Study ID Numbers: | 10-491-B, 44574 |
Study First Received: | December 6, 2010 |
Last Updated: | May 26, 2011 |
Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Chicago:
Desmoid Tumor Sirolimus Surgically-Resectable Desmoid Tumor |
Additional relevant MeSH terms:
Fibroma Fibromatosis, Aggressive Neoplasms, Fibrous Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Sirolimus Everolimus Antibiotics, Antineoplastic |
Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on October 18, 2012