Ganitumab in Locally Advanced Unresectable Adenocarcinoma of the Pancreas

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of AMG 479 or Placebo in Combination With Gemcitabine as First-line Therapy for Locally Advanced Unresectable Adenocarcinoma of the Pancreas

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.

Study Overview

• Status: Terminated
• Conditions: Adenocarcinoma of the Pancreas; Locally Advanced; Unresectable
• Intervention / Treatment: Drug: Gemcitabine; Drug: Placebo; Drug: AMG 479

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Research Site
  • Steyr, Austria, 4400
    • Research Site
  • Wien, Austria, 1090
    • Research Site
• Belgium
  • Edegem, Belgium, 2650
    • Research Site
  • La Louviere, Belgium, 7100
    • Research Site
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Olomouc, Czechia, 775 20
    • Research Site
  • Praha 10, Czechia, 100 34
    • Research Site
• Denmark
  • Herlev, Denmark, 2730
    • Research Site
• Germany
  • Hamburg, Germany, 20249
    • Research Site
• Hungary
  • Budapest, Hungary, 1097
    • Research Site
  • Debrecen, Hungary, 4012
    • Research Site
  • Miskolc, Hungary, 3526
    • Research Site
  • Szolnok, Hungary, 5004
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Research Site
  • Seoul, Korea, Republic of, 120-752
    • Research Site
  • Seoul, Korea, Republic of, 138-736
    • Research Site
  • Seoul, Korea, Republic of, 152-703
    • Research Site
• Poland
  • Lodz, Poland, 93-509
    • Research Site
  • Poznan, Poland, 60-569
    • Research Site
  • Warszawa, Poland, 02-097
    • Research Site
• Portugal
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
  • Samara, Russian Federation, 443031
    • Research Site
• Spain
  • Madrid, Spain, 28034
    • Research Site
  • Madrid, Spain, 28050
    • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guys Hospital
  • London, United Kingdom, W12 0HS
    • Research Site
  • Preston, United Kingdom, PR2 9HT
    • Research Site
• United States
  • California
    • San Francisco, California, United States, 94115
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo + Gemcitabine; Arm 2: AMG479-placebo IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle	Drug: Gemcitabine; Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.; Other Names: Gemzar; Drug: Placebo; Gemcitabine on Days 1, 8, and 15 followed by Placebo 20 mg/kg on days 1 and 15 of every 28 day cycle
Experimental: AMG 479 20 mg/kg + Gemcitabine; ARM 1: AMG 479 20mg/kg IV days 1 and 15 plus gemcitabine 1000mg/m2 IV days 1, 8, and 15 of a 28 day cycle.	Drug: Gemcitabine; Gemcitabine on days 1, 8, and 15, followed by placebo on days 1 and 15 of every 28 day cycle.; Other Names: Gemzar; Drug: AMG 479; 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 Names: gemcitabine = Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Endpoint is Progression-free Survival (PFS) as Defined as the Time From Randomization to Progression (Per RECIST v1.1) or Death.	The time from randomization to progression (per RECIST version 1.1) or death from any cause. Disease progression per RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.	From randomization to the date of either disease progression or death, up to 181 days progression or death

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	OS - time from study day 1 to death (by any cause)	Up to 181 days
Number of Participants With Adverse Events	Measured via CTCAE v3.0	Up to 4 months
Progression Free Survival Rate and Overall Survival Rate at at 3 and 6 Months, Objective Response Rate, Disease Control Rate	PFS rates - subjects with disease progression (PD) or death at the timepoint; OS rates - subjects alive at the timepoint; ORR - tumor response assessment of either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST); DCR - subjects with PR, CR, or SD Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed	Up to 181 days
Duration of Response	DOR - time from the first observation of an objective response (subjects with CR or PR) to the time of PD or death; Per RECIST: CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Disease progression=at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study; stable disease is disease that is not partial or progressed	Up to 181 days
Number of Participants With Anti-AMG 479 Antibodies	post-dose anti-AMG 479 antibody positive rate	Up to 181 days

Collaborators and Investigators

• Sponsor: NantBioScience, Inc.
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2012
• Primary Completion (Actual): November 27, 2012
• Study Completion (Actual): December 3, 2012

Study Registration Dates

• First Submitted: March 17, 2011
• First Submitted That Met QC Criteria: March 17, 2011
• First Posted (Estimated): March 18, 2011

Study Record Updates

• Last Update Posted (Actual): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: stage III; pancreas; Adenocarcinoma; pancreatic cancer; local; unresectable; stage II
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: 20080261; 2010-023978-39 (EudraCT Number)