Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer

Inclusion Criteria: * Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma * Not amenable to potentially curative surgical resection * At least 1 prior regimen of chemotherapy, preferably gemcitabine-based, for metastatic disease * Evidence of disease progression * Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan * Available archived tumor tissue (baseline core biopsies or surgical tumor blocks) * No diagnosis by fine-needle aspiration only * No known brain metastases * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (Karnofsky 70-100%) * White blood cell count (WBC) ≥ 3,000/mm³ * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL * Total bilirubin normal * Aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present) * Creatinine normal OR creatinine clearance ≥ 60 mL/min * Willingness to undergo 2 tumor biopsies, if required * Fertile patients must use 2 forms of contraception (i.e., barrier contraception and one other method of contraception) ≥ 4 weeks prior to, during, and for ≥ 12 months after completion of therapy * Negative pregnancy test * Not pregnant or nursing * Able to swallow pills * No patients with malabsorption syndrome or other condition that would interfere with intestinal absorption * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma secretase inhibitor RO4929097 * Not serologically positive for hepatitis A, B, or C * No history of liver disease, other forms of hepatitis, or cirrhosis * No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia other than chronic, stable atrial fibrillation * Psychiatric illness/social situations that would limit compliance with study requirements * No baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female) * No other malignancy within the past 5 years except curatively treated basal cell carcinoma of the skin or carcinoma in-situ of the uterine cervix * No combination antiretroviral therapy for HIV-positive patients * Recovered to \< Common Toxicity Criteria for Adverse Effects (NCI CTCAE) grade 2 toxicities from prior therapy * More than 3 weeks since prior chemotherapy for metastatic disease (6 weeks for carmustine or mitomycin C) * At least 4 weeks since prior radiotherapy * Concurrent low-molecular weight heparin (LMWH) or full-dose coumadin allowed * International normalized ratio (INR) must be monitored as clinically indicated * No other concurrent investigational agents * No concurrent strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers, including the following: * Strong inhibitors: Amiodarone, erythromycin, clarithromycin, grapefruit juice, isoniazid, ketoconazole, itraconazole, or nefazodone * Patients taken off strong inhibitors allowed provided they have ≥ 1-week washout period * Strong inducers: Carbamazepine, pentobarbital, phenobarbital, phenytoin, Rifabutin, Rifampin, or St. John wort * Patients taken off strong inducers allowed provided they have ≥ 2-week washout period * No concurrent antiarrhythmics or other medications known to prolong QTc