Ganitumab in Locally Advanced Unresectable Adenocarcinoma of the Pancreas

• Progression-free survival and overall survival rates at 3, 6, 9, 12, 18, and 24 months [ Time Frame: Approximately 23 months ] [ Designated as safety issue: No ]
• Objective response rate (complete or partial response) per RECIST v1.1 [ Time Frame: Approximately 23 months ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: Approximately 23 months ] [ Designated as safety issue: No ]

This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1).

Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.

This study is a phase 2, multicenter, randomized, double-blind, active placebo-controlled trial of AMG 479 or placebo in combination with gemcitabine as first-line therapy for locally advanced unresectable adenocarinoma of the pancreas. Approximately 150 subjects will be randomized in a 1:1 ratio to AMG 479 and gemcitabine, or gemcitabine and placebo. Randomization will be stratified by ECOG (0 or 1).

Gemcitabine will be given on days 1, 8, and 15, followed by AMG 479 on days 1 and 15 of every 28 day cycle. Treatment will continue until radiographic disease progression, unacceptable toxicity, withdrawal of consent, or start of a new anti-cancer therapy.

• Adenocarcinoma of the Pancreas
• Locally Advanced
• Unresectable

• Drug: Gemcitabine
  gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.
  Other Name: Gemzar
• Drug: AMG 479 + gemcitabine
  gemcitabine on days 1, 8, and 15, followed by AMG 479 20 mg/kg on days 1 and 15 of every 28 day cycle.
  Other Name: gemcitabine = Gemzar

• Active Comparator: Placebo + Gemcitabine
  Intervention: Drug: Gemcitabine
• Experimental: AMG 479 20 mg/kg + gemcitabine
  Intervention: Drug: AMG 479 + gemcitabine

Inclusion Criteria:

• Subjects must have histologically or cytologically confirmed locally advanced adenocarcinoma of the pancreas that is unresectable, per institutional practice
• Radiologically measurable and/or non-measurable disease as defined by RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
• Men or women >/= 18 years of age
• Adequate organ function

Exclusion Criteria:

• Early (stage I) or metastatic (stage IV) disease
• Islet cell, acinar cell carcinoma, non-adenocarcinoma, (eg, lymphoma, sarcoma, etc), adenocarcinoma originating from biliary tree or cystadenocarcinoma
• External biliary drain
• Currently treated or previously treated with biologic, small molecule, immunotherapy, chemotherapy (ie, including gemcitabine), or other agents for pancreatic cancer
• Currently treated or previously treated with radiotherapy, or chemoradiotherapy for pancreatic cancer