Intervention: Sirolimus
Trial phase: Phase 1 | Phase 2
ATC code: L01EG04 | L04AA10 | S01XA23
SMILES: COC1CC2CCC(C)C(O)(O2)C(=O)C(=O)N2CCCCC2C(=O)OC(C(C)CC2CCC(O)C(OC)C2)CC(=O)C(C)C=C(C)C(O)C(OC)C(=O)C(C)CC(C)C=CC=CC=C1C
Sex: All
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 9
Group description: Preoperative sirolimus:

loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligram)
starting 24 hours after the initial loading dose, subjects will receive a dose of 4 milligram/meters2 daily; Per Os (PO), by mouth days 2 through 28

Sirolimus: -Loading dose of 12 milligrams/meter2; Per Os (PO), by mouth day 1 (Max dose 12 milligrams)

-Starting 24 hours after the initial loading dose, patients will receive a dose of 4 milligrams/meter2 daily; Per Os (PO), by mouth days 2 through 28 (Max dose 4 milligram/day)
Eligibility criteria:
Inclusion Criteria:

Must be less than 30 years of age at time of original 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 and/or previously unresected 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 3 days 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 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 normal serum creatinine based on age/gender

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