Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis

* INCLUSION CRITERIA: 2.1.1.1 Patients must have histologically confirmed desmoid tumor confirmed by the Laboratory of Pathology, National Cancer Institute (NCI), that has progressed after receiving at least one line of standard treatment and that is not amenable to surgical resection or definitive radiation therapy. 2.1.1.2 Willingness to provide blood samples and 10 unstained slides or a tumor block for genetic research studies. 2.1.1.3 Any line of therapy with prior desmoid therapy, including radiotherapy, should have been completed at least 2 weeks before study entry and all toxicities must have resolved at least to eligibility levels. 2.1.1.4 Age greater than or equal 18 years; because no dosing or adverse event data are currently available on the use of PF-03084014 in patients \<18 years of age, children are excluded from this study, but may be eligible for future pediatric trials. 2.1.1.5 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal 2. 2.1.1.6 Life expectancy \> 3 months. 2.1.1.7 Patients must have normal organ and marrow function as defined below: * -absolute neutrophil count greater than or equal 1,500/mcL * -platelets greater than or equal 100,000/mcL * -total bilirubin less than or equal 1.5 times institutional upper limit of normal * -Aspartate aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/Alanine aminotransferase (ALT) Serum glutamic-pyruvic transaminase (SGPT) less than or equal 5 times institutional upper limit of normal * -creatinine \< 1.5 times institutional upper limit of normal OR * -creatinine clearance greater than or equal 60 mL/min/1.73 m(2) for patients with creatinine levels \>1.5 mg/dL * -hemoglobin greater than or equal 9 g/dL 2.1.1.8 Patients must be able to swallow whole tablets or capsules with no gastrointestinal (GI) condition affecting absorption; nasogastric or G-tube administration is not allowed. 2.1.1.9 The effects of PF-03084014 on the developing human fetus are unknown. For this reason and because \>=-secretase inhibitors are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for at least 6 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and 6 months after completion of study drug administration. 2.1.1.10 Ability to understand and the willingness to sign a written informed consent document. 2.1.1.11 Evidence of measurable disease by computed tomography (CT) scan. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal 20 mm by chest x-ray, as greater than or equal 10 mm with CT scan, or greater than or equal 10 mm with calipers by clinical exam. EXCLUSION CRITERIA: 2.1.2.1 Patients who are receiving any other investigational agents. Concurrent mediations that the patient is taking will be reviewed by the principal investigator (PI) to assess safety and eligibility. 2.1.2.2 Prior treatment with Gamma-secretase inhibitors or anti-notch antibody therapy. 2.1.2.3 Uncontrolled intercurrent illness including, but not limited to, serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 2.1.2.4 Corrected QT interval (QTc) interval of \>470 msec at study entry; congenital long QT syndrome. 2.1.2.5 Pregnant women are excluded from this study because PF-03084014 is a Gamma-secretase inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PF-03084014, breastfeeding should be discontinued if the mother is treated with PF-03084014. 2.1.2.6 Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow the tablet whole. Tablets must not be crushed or chewed; nasogastric or gastrostomy (G)-tube administration is not allowed. 2.1.2.7 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with PF-03084014. 2.1.3 Recruitment Strategies We have had multiple discussions with the Desmoid Tumor Research Foundation, Inc., who have various outreach efforts including patient meetings and webcasts. Senior executives of the Foundation have indicated strong interest in this trial and willingness to inform their members. We also have a network of referring physicians nationally that refers patients with solid tumors to our clinical program. Given our interest and trials for sarcomas, we have formed connections with centers that treat patients with mesenchymal malignancies. We will be informing all of these of the availability of this trial once it is open.