Erlotinib, Gemcitabine and Nab-Paclitaxel in Advanced Pancreatic Cancer

• Safety of drug combination assessed through dose limiting toxicities (DLTs) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
• Safety of drug combination assessed through Adverse Events (AEs) [ Time Frame: Monthly (to a maximum of 12 months) ] [ Designated as safety issue: No ]
• Evaluate erlotinib Pharmacokinetic (PK) trough concentrations (C24h) [ Time Frame: Days 29 (Cycle 2, Day 1) and 30 ] [ Designated as safety issue: No ]
• Objective Response Rate [ Time Frame: Monthly (to a maximum of 12 months) ] [ Designated as safety issue: No ]
  Response will be based on the RECIST v1.1 criteria. Patients with partial and complete response will be classified as "responders".
• Progression Free Survival (PFS) [ Time Frame: Monthly (to a maximum of 12 months) ] [ Designated as safety issue: No ]
  PFS will be calculated as the time from start of treatment until disease progression or death; patients who are still alive and free of progression at their last follow-up will be censored at that time.
• Overall Survival [ Time Frame: Monthly (to a maximum of 12 months) ] [ Designated as safety issue: No ]
  Survival will be calculated as the time from start of treatment until death of any cause, patients who are still alive at their last follow-up will be censored at that time.

• Assess safety of drug combination [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]
• Evaluate erlotinib PK in drug combination [ Time Frame: Single time point ] [ Designated as safety issue: No ]
• Preliminary efficacy of drug combination [ Time Frame: Monthly ] [ Designated as safety issue: No ]

This is a phase 1b study to evaluate the combination of gemcitabine and Tarceva (erlotinib) and nab-paclitaxel in patients with advanced pancreatic cancer.

This is a single-arm, phase 1b study to determine the maximum tolerated dose (MTD) of the combination of erlotinib (daily), gemcitabine (weekly), nab-paclitaxel (weekly) in patients with advanced pancreatic cancer.

• Drug: erlotinib
  administered orally
  Other Names:

  • Tarceva
  • OSI-774
• Drug: gemcitabine
  administered intravenously
• Drug: nab-paclitaxel
  administered intravenously

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
• Predicted life expectancy of >= 12 weeks
• Previous surgery
• Histologically or cytologically confirmed, measurable, locally advanced, unresectable or metastatic pancreatic adenocarcinoma
• No prior therapy for pancreatic cancer

• Adequate organ and marrow function

  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Total bilirubin <= institutional upper limits of normal
  • AST (SGOT)/ALT(SGPT) <= 2 x institutional upper limits of normal
  • Serum creatine <= 1.5 x upper limits of normal
• Negative pregnancy test
• Informed consent
• Patient must agree not to smoke while on study

Exclusion Criteria:

• Significant history of cardiac disease unless the disease is well controlled
• Active or uncontrolled infections or serious illness or medical conditions that could interfere with the patient's ongoing participation in study
• History of any psychiatric condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent
• History of smoking within the previous 14 days before enrollment or positive cotinine test at baseline
• Pregnant or breast-feeding females
• Symptomatic brain metastases that are not stable, that require steroids, that are potentially life-threatening, or that have required radiation within the last 14 days
• History of allergic reactions attributed to compounds of similar chemical or biological composition to the study drugs