Clinical trial NCT00902291: A Study of AGS-1C4D4 Given in Combination With Gemcitabine in Subjects With Metastatic Pancreatic Cancer
Official title: A Global, Multi-center, Open-label, Phase 2 Study of AGS-1C4D4 Given in Combination With Gemcitabine in Subjects With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Pancreatic Ductal
Pancreatic Cancer
Pancreatic Disease
Keywords: Clinical Trial, Phase II
Combination Drug Therapy
Gemcitabine
AGS-1C4D4
Pancreatic Cancer
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Agensys, Inc.
First posted: 2009-05-15
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival rate at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Throughout treatment period and post-treatment every 2 months until death, or subject discontinues the study
measure: Progression free survival (PFS)
timeFrame: Throughout treatment period or post-treatment every 2 months until disease progression or death, respectively, or subject discontinues the study
measure: Change in level of serum tumor marker CA 19-9
timeFrame: Week 1, Week 4, Week 7 and every 3 weeks during the extended treatment period
measure: Incidence of anti-AGS-1C4D4 antibody formation
timeFrame: Week 1, Week 7 and every 8 weeks during the extended treatment period
measure: Objective Response Rate (Partial Response or better per RECIST criteria version 1.1
timeFrame: Week 8, and every 8 weeks during the extended treatment period
measure: Disease Control (Stable Disease or better per RECIST criteria)
timeFrame: Week 8, and every 8 weeks during the extended treatment period
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Boynton Beach
country: United States
facility: Palm Beach Institute of Hematology and Oncology
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Baton Rouge
country: United States
facility: Medical Oncology LLC
state: Louisiana
city: Annapolis
country: United States
facility: Annapolis Oncology Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Virginia G. Piper Cancer Center
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: Regional Oncology Center
state: New York
city: Portland
country: United States
facility: Kaiser Permanente Northwest Region Oncology Hematology
state: Oregon
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Div. of Medical Oncology
state: Tennessee
city: Lynchburg
country: United States
facility: Alan B. Pearson Regional Cancer Center Lynchburg Hematology Oncology Clinic
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Clermont-Ferrand
country: France
facility: Chu Estaing
city: Le Mans Cedex
country: France
facility: Centre Jean Bernard, Oncologie médicale
city: Lille
country: France
facility: Centre Régional de Lutte Contre le Cancer-Centre Oscar Lambret
city: Pessac
country: France
facility: Hôpital du Haut Lèvêque, Service d'Hepato Gastroentérologie
city: Poitiers Cedex
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Arkhangelsk
country: Russian Federation
facility: State Institution of Healthcare "Arkhangelsk Regional Clinical Oncology Dispensary"
city: Ivanovo
country: Russian Federation
facility: Regional Oncology Dispensary
city: Kazan
country: Russian Federation
facility: Clinical Oncology Dispensary of Republic of Tatarstan
city: Kuzmolovo
country: Russian Federation
facility: State Healthcare Institution "Leningrad Regional Oncologic Dispensary"
city: Moscow
country: Russian Federation
facility: Non-state Healthcare Institution N.A. Semashko Central Clinical Hospital #2 of JSC "Russian Railway"
city: Obninsk
country: Russian Federation
facility: Medical Radiology Research Center of Russian Medical Academy
city: Omsk
country: Russian Federation
facility: State Healthcare Institution of Omsk Region "Clinical Oncologic Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: State Educational Institution "S.M. Kirov Military Medical Academy of Ministry of Defense of Russia"
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg State Healthcare Institution "Municipal Clinical Oncology Dispensary"
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona, Servicio de Oncologia
city: Madrid
country: Spain
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud, Servicio Oncologia
Study officials:
affiliation: Agensys, Inc.
name: Chief Medical Officer
role: STUDY_DIRECTOR
References:
citation: Wolpin BM, O'Reilly EM, Ko YJ, Blaszkowsky LS, Rarick M, Rocha-Lima CM, Ritch P, Chan E, Spratlin J, Macarulla T, McWhirter E, Pezet D, Lichinitser M, Roman L, Hartford A, Morrison K, Jackson L, Vincent M, Reyno L, Hidalgo M. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer. Ann Oncol. 2013 Jul;24(7):1792-1801. doi: 10.1093/annonc/mdt066. Epub 2013 Feb 28.