AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer
22. dubna 2019 aktualizováno: Pfizer
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
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.
Přehled studie
Postavení
Dokončeno
Podmínky
Intervence / Léčba
Typ studie
Intervenční
Zápis (Aktuální)
111
Fáze
- Fáze 2
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Gent, Belgie, 9000
- Universitair Ziekenhuis Gent/Dienst Gastroenterologie
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Marseille, Francie, 13005
- Hôpital La Timone
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Paris Cedex 13, Francie, 75651
- Hopital de La Pitie Salpetriere
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Toulouse, Francie, 31052
- Institut Claudius Regaud
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Saint Herblain Cedex
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Saint-Herblain, Saint Herblain Cedex, Francie, 44805
- Service Oncologie Medicale
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Milano, Itálie, 20133
- Fondazione IRCCS, Istituto Nazionale Tumori, Oncologia Medica B
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Roma, Itálie, 00168
- Unita Operativa, Oncologia Medica, Istituto di Medicina Interna e Geriatria
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Alberta
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Edmonton, Alberta, Kanada, T6G 1Z2
- Cross Cancer Institute
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Manitoba
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Winnipeg, Manitoba, Kanada, R3E 0V9
- CancerCare Manitoba
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Winnipeg, Manitoba, Kanada, R2H 2A6
- Cancer Care Manitoba
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Ontario
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Sault Ste Marie, Ontario, Kanada, P6A 2C4
- Sault Area Hospital
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Toronto, Ontario, Kanada, M5G 2M9
- Princess Margaret Hospital
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Quebec
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Montreal, Quebec, Kanada, H2X 3J4
- CHUM, Hopital Saint-Luc
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Berlin, Německo, 13353
- Medizinische Klinik mit Schwerpunkt Haematologie und Onkologie, Charité-Universitaetsmedizin Berlin
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Edinburgh, Spojené království, EH4 2XU
- Western General Hospitals Nhs Trust
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London, Spojené království, W12 OHS
- Hammersmith Hospital
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Hampshire
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Southampton, Hampshire, Spojené království, SO16 6YD
- Cancer Research UK Clinical Centre
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Leicestershire
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Leicester, Leicestershire, Spojené království, LE1 5WW
- Department of Cancer Studies & Molecular Medicine
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California
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Antioch, California, Spojené státy, 94509
- East Bay Medical Oncology/Hematology Medical Associates Inc.
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Berkeley, California, Spojené státy, 94704
- Alta Bates Comprehensive Cancer Center
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Concord, California, Spojené státy, 94520
- Bay Area Cancer Research Group
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Concord, California, Spojené státy, 94520
- East Bay Medical Oncology/Hematology Medical Associates, Inc.
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Connecticut
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Stamford, Connecticut, Spojené státy, 06902-3628
- Hematology Oncology, P.C.
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Florida
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Miami, Florida, Spojené státy, 33136
- University of Miami Hospital & Clinics
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Miami, Florida, Spojené státy, 33136
- Jackson Memorial Hospital & Clinics
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Tampa, Florida, Spojené státy, 33612-9497
- H Lee Moffitt Cancer Center & Research Institute
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Maine
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Biddeford, Maine, Spojené státy, 04005
- Maine Center for Cancer Medicine and Blood Disorders
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Brunswick, Maine, Spojené státy, 04011
- Maine Center for Cancer Medicine and Blood Disorders
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Scarborough, Maine, Spojené státy, 04074
- Maine Center for Cancer Medicine and Blood Disorders
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Missouri
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Saint Louis, Missouri, Spojené státy, 63141
- Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research
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Washington, Missouri, Spojené státy, 63090
- Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research
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Nebraska
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Lincoln, Nebraska, Spojené státy, 68510
- Southeast Nebraska Cancer Center, Southeast Nebraska Hematology and Oncology Consultants, P.C.
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North Carolina
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Winston-Salem, North Carolina, Spojené státy, 27103
- Piedmont Hematology Oncology Association
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Winston-Salem, North Carolina, Spojené státy, 27292
- Piedmont Hematology Oncology Associates
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Wisconsin
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Madison, Wisconsin, Spojené státy, 53792
- University of Wisconsin Hospital and Clinics
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Barcelona, Španělsko, 08036
- Hospital Clinic i Provincial de Barcelona
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Barcelona, Španělsko, 08035
- Hospital Universitario Vall d´Hebron
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Sevilla, Španělsko, 41013
- Hospital Universitario Virgen Del Rocio
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let a starší (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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)
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Aktivní komparátor: Gemcitabin
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Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks
Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
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Experimentální: Axitinib [AG-013736] plus gemcitabine
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Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks
Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Axitinib (AG-013736) 5 mg tablet orally BID starting from Day 1 of Cycle 1, in cycles of 4 weeks.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Overall Survival (OS)
Časové okno: Baseline of Phase 2 to death or until at least 1 year after the randomization of the last participant
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Time in days from randomization to date of death due to any cause.
OS was calculated as the death date minus the date of randomization plus 1. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
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Baseline of Phase 2 to death or until at least 1 year after the randomization of the last participant
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Dose Confirmation of Axitinib (AG-013736) on Basis of Number of Participants With Dose Limiting Toxicity (DLT)
Časové okno: Phase 1 baseline up to Week 4
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Dose of axitinib (AG-013736) was confirmed if not more than 1 out of 6 participants experienced a DLT during first cycle.
DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (>=) Gr 3 anemia or non hematological toxicities for >= 7 days (except alopecia) or >= Gr 1 hemoptysis or >=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.
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Phase 1 baseline up to Week 4
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Dose Confirmation of Gemcitabine on Basis of Number of Participants With Dose Limiting Toxicity (DLT)
Časové okno: Phase 1 Baseline up to Week 4
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Dose of gemcitabine was confirmed if not more than 1 out of 6 participants experienced a DLT during first cycle.
DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (>=) Gr 3 anemia or non hematological toxicities for >= 7 days (except alopecia) or >= Gr 1 hemoptysis or >=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity.
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Phase 1 Baseline up to Week 4
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Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)
Časové okno: 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
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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
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Area Under the Curve From Time Zero to 24 Hours [AUC (0-24)] of Axitinib (AG-013736)
Časové okno: 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
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AUC (0-24) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to 24 hours (0-24).
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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
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Time to Reach Maximum Observed Plasma Concentration (Tmax) of Axitinib (AG-013736)
Časové okno: 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
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Tmax was based on the actual time points when the samples were collected.
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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
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Plasma Decay Half-life (t1/2) of Axitinib (AG-013736)
Časové okno: 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
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Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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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
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Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
Časové okno: 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
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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
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Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] of Gemcitabine
Časové okno: 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
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AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).
It is obtained from AUC (0 - t) plus AUC (t - ∞).
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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
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Plasma Decay Half-life (t1/2) of Gemcitabine
Časové okno: 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
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Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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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
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Population Pharmacokinetics of Axitinib (AG-013736) in Phase 2
Časové okno: 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
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Data for this outcome measure are not reported here because the analysis population includes participants who were not enrolled in this study.
ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
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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
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Percentage of Participants With Overall Response (OR)
Časové okno: Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks
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Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).
Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
CR are defined as the disappearance of all lesions (target and/or non-target).
PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum of longest dimensions.
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Phase 2 baseline to disease progression or discontinuation from study, assessed every 8 weeks up to 80 weeks
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Duration of Response (DR)
Časové okno: Phase 2 baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 80 weeks
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Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cancer.
Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
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Phase 2 baseline to disease progression or discontinuation from study due to any cause, assessed every 8 weeks up to 80 weeks
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Progression-free Survival (PFS)
Časové okno: Phase 2 baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 80 weeks
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Time in days from randomization to first documentation of objective tumor progression or death due to any cause.
PFS was calculated as first event date minus the date of randomization plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
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Phase 2 baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 80 weeks
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One Year Survival Probability
Časové okno: 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
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One year survival probability was defined as the probability of survival at one year after the date of randomization based on the Kaplan Meier estimate.
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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
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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
Časové okno: 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).
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EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties).
Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent').
Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Change from baseline=Cycle/Day score minus baseline score.
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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).
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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
Časové okno: 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).
|
QLQ-PAN26 consists of 26 questions (Qs) relating to disease symptoms, treatment (Tx) side effects and emotional issues specific to pancreatic cancer (PC).
Questions include on altered bowel habits, pain, dietary changes, disease and Tx-related symptoms and issues related to the emotional and social well-being of participants with PC.
All 26 Qs are answered on 4-point Likert scale ranging from '1=not at all' to 4='very much' and subsequently transformed into scales that range from 0-100.
Higher scores on functioning scales=better functioning; higher scores on the symptom scales=more symptoms.
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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).
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
5. července 2005
Primární dokončení (Aktuální)
14. března 2008
Dokončení studie (Aktuální)
14. března 2008
Termíny zápisu do studia
První předloženo
13. září 2005
První předloženo, které splnilo kritéria kontroly kvality
13. září 2005
První zveřejněno (Odhad)
22. září 2005
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
14. května 2019
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
22. dubna 2019
Naposledy ověřeno
1. dubna 2019
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Nemoci trávicího systému
- Novotvary
- Novotvary podle místa
- Onemocnění endokrinního systému
- Novotvary trávicího systému
- Novotvary endokrinních žláz
- Onemocnění slinivky břišní
- Novotvary pankreatu
- Fyziologické účinky léků
- Molekulární mechanismy farmakologického působení
- Antiinfekční látky
- Antivirová činidla
- Inhibitory enzymů
- Antimetabolity, Antineoplastika
- Antimetabolity
- Antineoplastická činidla
- Imunosupresivní látky
- Imunologické faktory
- Inhibitory proteinkinázy
- Gemcitabin
- Axitinib
Další identifikační čísla studie
- A4061016
- 2005-000053-30 (Číslo EudraCT)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
Pfizer will provide access to individual de-identified participant data and related study documents (e.g.
protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.
Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .