RO4929097 Before Surgery in Treating Patients With Pancreatic Cancer

This is an interventional treatment trial for Adenocarcinoma of the Pancreas Read More

Inclusion Criteria:

• Histologically or cytologically confirmed pancreatic adenocarcinoma

  • T1-3, N0-1, and M0 disease

• Surgically resectable disease confirmed by a surgeon experienced in pancreatic surgery

  • No borderline resectable disease defined as any of the following:

    • Tumors with severe unilateral or bilateral SMV/portal involvement impingement
    • Abutment (or) encasement of hepatic artery
    • SMA or celiac encasement (or) presence of SMV occlusion by tumor
• No metastatic disease
• ECOG performance status 0-1
• Life expectancy > 6 months
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 2 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 2 mg/dL
• Calcium, magnesium, phosphorous, and potassium normal
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective barrier-method contraception 4 weeks before, during, and for ≥ 12 months after completion of treatment
• Able to swallow tablets
• No 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 or other agents used in the study

• No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation

  • Grade 1 hyponatremia with sodium ≤ 131 mg/dL is permissible

• 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)

• Patients with a prior cancer with evidence of active cancer are excluded from this study

  • Patients with a prior cancer are permitted to enter this study as long as there is no documented evidence of active malignancy
• No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, and hypokalemia
• No symptomatic congestive heart failure, unstable angina pectoris, and a history of torsades de pointes or other significant cardiac arrhythmias
• No requirement for antiarrhythmics or other medications known to prolong QTc
• No other concurrent anticancer agents or therapies
• Recovered to < grade 2 toxicity related to prior therapy
• No prior chemotherapy or radiotherapy for pancreatic cancer
• No other concurrent investigational agents
• No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®), ketoconazole, or grapefruit juice
• No concurrent strong inducers or inhibitors of CYP3A4
• No concurrent combination antiretroviral therapy for HIV-positive patients