Gamma-Secretase Inhibitor RO4929097 in Treating Patients With Metastatic or Unresectable Solid Malignancies

Inclusion Criteria:

* Histologically or cytologically confirmed solid malignancy

  * Metastatic or unresectable disease
  * Standard curative or palliative measures do not exist or are no longer effective
* 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 70-100%)
* Life expectancy \> 12 weeks
* Leukocytes ≥ 3,000/mm\^3
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL
* Total bilirubin normal
* AST/ALT ≤ 2.5 times upper limit of normal
* Serum creatinine normal OR creatinine clearance ≥ 60 mL/min
* No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia, defined as \< lower limit of normal despite adequate electrolyte supplementation
* QTc ≤ 450 msec in males and a QTc ≤ 470 in females, as measured by ECG using Bazett's formula
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use 2 forms of contraception (i.e., barrier contraception and 1 other method of contraception) for ≥ 4 weeks before, during, and for ≥ 12 months after completion of study treatment
* Willing to undergo 2 tumor biopsies (unless medically contraindicated)
* Able to swallow medication
* No malabsorption syndrome or other condition that would interfere with intestinal absorption
* No diarrhea ≥ grade 2 not under control with standard antidiarrhea medications
* 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 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
  * A history of torsades de pointes
  * Recurrent syncope without known etiology
  * Sudden unexpected death
* Female patients may not donate ova during or after study treatment
* No blood donation during and for ≥ 12 months after completion of study treatment
* No serologic positivity for hepatitis A, B, or C; history of liver disease; or other forms of hepatitis or cirrhosis
* No HIV-positive patients on combination antiretroviral therapy
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to gamma-secretase inhibitor RO4929097 or other agents used in this study
* No other concurrent agents or therapies administered with the intent to treat the patient's malignancy
* No prior gamma-secretase inhibitors
* Any number of prior treatment regimens allowed
* At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for prior carmustine or mitomycin C)

  * Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy for symptomatic palliation
* Recovered from the adverse events due to prior therapy to \< CTCAE grade 2 (except alopecia)
* No other concurrent investigational agents
* No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450, including warfarin sodium (Coumadin®)
* 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, grapefruit, or grapefruit juice
* No antiarrhythmics or other concurrent medications with known potential to prolong QT interval