A Study of AGS-1C4D4 Given in Combination With Gemcitabine in Subjects With Metastatic Pancreatic Cancer

Phase 2

Completed

Conditions: Carcinoma, Pancreatic Ductal
Pancreatic Disease
Pancreatic Cancer

Interventions: Biological: Gemcitabine
Biological: AGS-1C4D4

Registration Number: NCT00902291

Lead Sponsor: Astellas Pharma Inc

Brief Summary: A study to evaluate AGS-1C4D4 administered in combination with Gemcitabine chemotherapy in subjects with Metastatic Pancreatic Cancer.

Detailed Description: A disease assessment will be performed at study week 8 (± 3 days) by the investigator. The assessment will be based both on changes in clinical symptoms, and radiographic images. Subjects without evidence of disease progression may continue to receive treatment based on their original treatment assignment until disease progression or intolerability. Disease assessments will be performed every 8 weeks during the extended period. A safety follow-up visit will occur 4 weeks after the last dose infusion of AGS-1C4D4 and/or gemcitabine.

Post-Treatment: Subjects terminating from protocol therapy for reasons unrelated to documented disease progression will be followed by telephone contact every 2 months until they begin a new anticancer therapy, their disease progresses, they die, become lost to follow-up or withdrawal consent for further follow-up, whichever of these events occurs first.

Overall survival: All subjects will be followed by telephone contact every 2 months until death, loss to follow-up, or withdrawal of consent, whichever of these events occurs first.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 205

Inclusion Criteria

Pathologically confirmed metastatic adenocarcinoma of the pancreas (AJCC Stage IV). Subjects with islet cell neoplasms are excluded
Non-measurable or measurable disease based on the RECIST criteria
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Life expectancy of > 3 months
Hematologic function, as follows:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9 g/dL (transfusion independent)
Renal function, as follows:
- Creatinine ≤ 2.0 mg/dL
Hepatic function, as follows:
- Aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases.
- Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases
- Bilirubin ≤ 2 x ULN
INR < 1.3 (or ≤ 3 if on warfarin for therapeutic anti-coagulation)

Exclusion Criteria

Prior systemic therapy for metastatic pancreatic cancer
- Subjects who have received adjuvant treatment with gemcitabine and who had relapse metastatically are allowed
- Subjects with advanced local disease who have received treatment with gemcitabine and in whom progression has been observed with the onset of metastases less than 6 months are excluded
Chemotherapy and/or radiation within 4 weeks of study enrollment
Prior monoclonal antibody therapy within 60 days of study enrollment
Known brain or leptomeningeal disease
History of other primary malignancy, unless:
- Curatively resected non-melanomatous skin cancer
- Other malignancy curatively treated with no known active disease present and no treatment administered for the last 3 years
Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System)
Use of any investigational product within 4 weeks of study enrollment
Major surgery (that requires general anesthesia) within 4 weeks before study enrollment
Women who are pregnant (confirmed by positive pregnancy test) or lactating
Man or woman of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for 4 weeks after the last AGS-1C4D4 and/or gemcitabine infusion administration
Subject known to be human immunodeficiency, hepatitis B or hepatitis C virus positive
Active serious infection not controlled with antibiotics

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1. Gemcitabine monotherapy	Gemcitabine	-
2. Gemcitabine plus AGS-1C4D4	AGS-1C4D4	-
2. Gemcitabine plus AGS-1C4D4	Gemcitabine	-

Primary Outcome Measures

Name	Time	Method
Survival rate at 6 months	6 months

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Throughout treatment period and post-treatment every 2 months until death, or subject discontinues the study
Incidence of anti-AGS-1C4D4 antibody formation	Week 1, Week 7 and every 8 weeks during the extended treatment period
Change in level of serum tumor marker CA 19-9	Week 1, Week 4, Week 7 and every 3 weeks during the extended treatment period
Disease Control (Stable Disease or better per RECIST criteria)	Week 8, and every 8 weeks during the extended treatment period
Progression free survival (PFS)	Throughout treatment period or post-treatment every 2 months until disease progression or death, respectively, or subject discontinues the study
Objective Response Rate (Partial Response or better per RECIST criteria version 1.1	Week 8, and every 8 weeks during the extended treatment period

Trial Locations

Locations (35): University of California San Diego Medical Center
🇺🇸
La Jolla, California, United States
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
Juravinski Cancer Centre
🇨🇦
Hamilton, Ontario, Canada
Hôpital Charles Nicolle
🇫🇷
Rouen, France
Medical Radiology Research Center of Russian Medical Academy
🇷🇺
Obninsk, Russian Federation
State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
🇷🇺
Arkhangelsk, Russian Federation
Medical Oncology LLC
🇺🇸
Baton Rouge, Louisiana, United States
Chu Estaing
🇫🇷
Clermont-Ferrand, France
Hôpital du Haut Lèvêque, Service d'Hepato Gastroentérologie
🇫🇷
Pessac, France
Regional Oncology Dispensary
🇷🇺
Ivanovo, Russian Federation
Saint Petersburg State Healthcare Institution "Municipal Clinical Oncology Dispensary"
🇷🇺
St. Petersburg, Russian Federation
Hospital Virgen de la Salud, Servicio Oncologia
🇪🇸
Toledo, Spain
Centre Régional de Lutte Contre le Cancer-Centre Oscar Lambret
🇫🇷
Lille, France
State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"
🇷🇺
Omsk, Russian Federation
Non-state Healthcare Institution N.A. Semashko Central Clinical Hospital #2 of JSC "Russian Railway"
🇷🇺
Moscow, Russian Federation
Hospital Clinic i Provincial de Barcelona, Servicio de Oncologia
🇪🇸
Barcelona, Spain
Centre Jean Bernard, Oncologie médicale
🇫🇷
Le Mans Cedex, France
State Educational Institution "S.M. Kirov Military Medical Academy of Ministry of Defense of Russia"
🇷🇺
Saint Petersburg, Russian Federation
State Healthcare Institution "Leningrad Regional Oncologic Dispensary"
🇷🇺
Kuzmolovo, Russian Federation
Clinical Oncology Dispensary of Republic of Tatarstan
🇷🇺
Kazan, Russian Federation
University of Miami
🇺🇸
Miami, Florida, United States
Dana Farber Cancer Center
🇺🇸
Boston, Massachusetts, United States
Virginia G. Piper Cancer Center
🇺🇸
Minneapolis, Minnesota, United States
Kaiser Permanente Northwest Region Oncology Hematology
🇺🇸
Portland, Oregon, United States
Palm Beach Institute of Hematology and Oncology
🇺🇸
Boynton Beach, Florida, United States
Annapolis Oncology Center
🇺🇸
Annapolis, Maryland, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Regional Oncology Center
🇺🇸
Syracuse, New York, United States
Baptist Regional Cancer Center
🇺🇸
Knoxville, Tennessee, United States
Cancer Centers of the Carolinas
🇺🇸
Greenville, South Carolina, United States
Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
Vanderbilt University Medical Center, Div. of Medical Oncology
🇺🇸
Nashville, Tennessee, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Alan B. Pearson Regional Cancer Center Lynchburg Hematology Oncology Clinic
🇺🇸
Lynchburg, Virginia, United States
Centre Hospitalier Universitaire de Poitiers
🇫🇷
Poitiers Cedex, France