Clinical trial NCT00219557: AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer
Official title: A RANDOMIZED PHASE 2 STUDY OF THE ANTI-ANGIOGENESIS AGENT AG-013736 IN COMBINATION WITH GEMCITABINE IN PATIENTS WITH CHEMOTHERAPY-NAIVE ADVANCED PANCREATIC CANCER PRECEDED BY A PHASE 1 PORTION
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Neoplasms
Keywords: Randomized Phase 2 Study of AG-013736 in Combination with Gemcitabine versus Gemcitabine Alone in Advanced Pancreatic Cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2005-09-22
Enrollment: 111
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: This is a Phase 2 study being conducted at multiple centers in the United States, Europe and Canada. Patients having pancreatic cancer that is locally advanced or that has spread to other parts of the body (i.e., metastatic) are eligible to participate. Patients must have not had any prior systemic treatment for advanced disease. The purpose of the study is to test whether the angiogenesis inhibitor Axitinib \[AG-013736\] in combination with gemcitabine is an effective treatment for advanced pancreatic cancer vs. gemcitabine alone by overall survival.


Eligibility criteria: Inclusion Criteria:

* patients with advanced (localized but surgically unresectable or metastatic) histologically/cytologically proven epithelial cancer of the exocrine pancreas
* no prior therapy for metastatic disease

Exclusion Criteria:

* patients with locally advanced disease who are candidates for radiation therapy.
* uncontrolled brain metastases (a controlled brain metastasis must be previously treated, asymptomatic, and without growth for 4 months)

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline of Phase 2 to death or until at least 1 year after the randomization of the last participant
Secondary outcomes:
measure: Dose Confirmation of Axitinib (AG-013736) on Basis of Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: Phase 1 baseline up to Week 4
measure: Dose Confirmation of Gemcitabine on Basis of Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: Phase 1 Baseline up to Week 4
measure: Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hours (hr) post-dose on Day 15 of Phase 1 Cycle 1
measure: Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Axitinib (AG-013736)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib (AG-013736)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1
measure: Plasma Decay Half-life (t1/2) of Axitinib (AG-013736)
timeFrame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3.5, 4.5, 9.5, and 12.5 hr post-dose on Day 15 of Phase 1 Cycle 1
measure: Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
timeFrame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Gemcitabine
timeFrame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1
measure: Plasma Decay Half-life (t1/2) of Gemcitabine
timeFrame: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9 and 12 hr after start of infusion on Day 15 of Phase 1 Cycle 1
measure: Population Pharmacokinetics of Axitinib (AG-013736) in Phase 2
timeFrame: Phase 2 Day 1 (Pre-dose), Day 29, Day 57 and then every 8 weeks until disease progression or discontinuation from study or up to 80 weeks
measure: Percentage of Participants With Overall Response (OR)
timeFrame: Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks
measure: Duration of Response (DR)
timeFrame: Phase 2 baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 80 weeks
measure: Progression-free Survival (PFS)
timeFrame: Phase 2 baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 80 weeks
measure: One Year Survival Probability
timeFrame: Phase 2 baseline to disease progression or death due to any cause or at least 1 year after the first dose for the last participant
measure: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score at Day 1 of Every Cycle and End of Study
timeFrame: Phase 2 baseline [Day (D)1 of Cycle (C)1], Day 1 of all subsequent cycles up to Cycle 14 and end of study (EoS).
measure: Change From Baseline in 26-item Pancreatic Cancer-specific Quality of Life Questionnaire (QLQ-PAN26) Score at Day 1 of Every Cycle and End of Study
timeFrame: Phase 2 baseline [Day (D) 1 of Cycle (C)1], Day 1 of all subsequent cycles up to Cycle 14 and end of study (EoS).
Other outcomes:
Locations:
city: Antioch
country: United States
facility: East Bay Medical Oncology/Hematology Medical Associates Inc.
state: California
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Concord
country: United States
facility: Bay Area Cancer Research Group
state: California
city: Concord
country: United States
facility: East Bay Medical Oncology/Hematology Medical Associates, Inc.
state: California
city: Stamford
country: United States
facility: Hematology Oncology, P.C.
state: Connecticut
city: Miami
country: United States
facility: Jackson Memorial Hospital & Clinics
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital & clinics
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Biddeford
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Brunswick
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Saint Louis
country: United States
facility: Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research
state: Missouri
city: Washington
country: United States
facility: Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research
state: Missouri
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center, Southeast Nebraska Hematology and Oncology Consultants, P.C.
state: Nebraska
city: Winston-Salem
country: United States
facility: Piedmont Hematology Oncology Association
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Hematology Oncology Associates
state: North Carolina
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent/Dienst Gastroenterologie
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Sault Ste Marie
country: Canada
facility: Sault Area Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM, Hopital Saint-Luc
state: Quebec
city: Saint-Herblain
country: France
facility: Service Oncologie Medicale
state: Saint Herblain Cedex
city: Marseille
country: France
facility: Hopital La Timone
city: Paris Cedex 13
country: France
facility: Hopital de la Pitie Salpetriere
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Berlin
country: Germany
facility: Medizinische Klinik mit Schwerpunkt Haematologie und Onkologie, Charité-Universitaetsmedizin Berlin
city: Milano
country: Italy
facility: Fondazione IRCCS, Istituto Nazionale Tumori, Oncologia Medica B
city: Roma
country: Italy
facility: Unita Operativa, Oncologia Medica, Istituto di Medicina Interna e Geriatria
city: Barcelona
country: Spain
facility: Hospital Universitario Vall D´Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Southampton
country: United Kingdom
facility: Cancer Research Uk Clinical Centre
state: Hampshire
city: Leicester
country: United Kingdom
facility: Department of Cancer Studies & Molecular Medicine
state: Leicestershire
city: Edinburgh
country: United Kingdom
facility: Western General Hospitals Nhs Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Letourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet. 2008 Jun 21;371(9630):2101-8. doi: 10.1016/S0140-6736(08)60661-3. Epub 2008 May 29.