Gamma-Secretase Inhibitor RO4929097 and Gemcitabine Hydrochloride in Treating Patients With Advanced Solid Tumors

Inclusion Criteria:

* Meets one of the following sets of criteria:

  * Histologically and/or cytologically confirmed solid malignancy

    * Metastatic or unresectable disease
    * Disease for which standard curative or palliative measures do not exist or are no longer effective
  * Histologically and/or cytologically confirmed adenocarcinoma of the pancreas (for patients in the expansion cohort)

    * Locally advanced or metastatic disease
    * No prior chemotherapy for advanced disease
* Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
* No known brain metastases
* ECOG performance status (PS) 0-1 (Karnofsky PS 60-100%)
* Life expectancy \> 12 weeks
* Hemoglobin ≥ 90 g/L (or ≥ 9 g/dL)
* Leukocytes ≥ 3,000/mm\^3
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1.25 times upper limit of normal (ULN)
* AST/ALT ≤ 1.5 times ULN
* Serum creatinine =\< ULN OR creatinine clearance ≥ 60 mL/min
* No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit of normal despite adequate electrolyte supplementation
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use two forms of adequate contraception (i.e., barrier contraception and one other method of contraception) for ≥ 4 weeks before, during, and for ≥ 12 months after completion of study treatment
* Able to swallow medication
* No malabsorption syndrome or other condition that would interfere with intestinal absorption
* No uncontrolled concurrent 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 or social situations that would limit compliance with study requirements
* No baseline QTc \> 450 msec (for male patients) or \> 470 msec (for female patients)
* No history of risk factors for QT interval prolongation including, but not limited to, a family or personal history of any of the following:

  * Long QT syndrome
  * Recurrent syncope without known etiology
  * Sudden unexpected death
* No history of torsade de pointes or other significant cardiac arrhythmias or the need for concomitant meds with known potential to prolong QT interval or antiarrhythmics
* No diarrhea ≥ grade 2 not under control with standard anti-diarrhea medications
* No serologic positivity for hepatitis A, B, or C
* No history of liver disease or other forms of hepatitis or cirrhosis
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or to gemcitabine hydrochloride
* Female patients may not donate ova during or after completion of study treatment
* Male patients may not donate sperm during and for ≥ 12 months after completion of study treatment
* Patients may not donate blood during and for ≥ 12 months after completion of study treatment
* No other concurrent investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
* Any number of prior therapies allowed
* No prior therapy with a Notch inhibitor
* At least 4 weeks since prior radiotherapy, chemotherapy, or systemic therapy (6 weeks if the last regimen included nitrosourea or mitomycin C) and recovered

  * Exceptions may be made for low-dose, non-myelosuppressive radiotherapy for symptomatic palliation
* Patients in the expansion cohort must meet the following criteria:

  * No prior chemotherapy for advanced disease except for fluorouracil (with or without folinic acid) or gemcitabine hydrochloride given concurrently with radiotherapy as a "radiosensitizer"
  * At least 6 months since prior adjuvant gemcitabine hydrochloride
  * Prior radiotherapy for the management of local disease allowed provided \> 4 weeks have elapsed since the last radiation treatment and all toxicities have resolved
  * Patients who have had radiotherapy to their sole site of disease are eligible provided they have documented progression of that lesion before study registration
* Recovered from side effects of previous systemic anticancer therapy to ≤ CTCAE grade 2
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
* No concurrent medications with known potential to prolong QT interval
* No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4
* No concurrent medications or food that may interfere with the metabolism of gamma-secretase inhibitor RO4929097, including ketoconazole and grapefruit or grapefruit juice
* No other concurrent investigational agents