AG-013736 In Combination With Gemcitabine Versus Gemcitabine Alone For Patients With Metastatic Pancreatic Cancer
22 de abril de 2019 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
111
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Berlin, Alemania, 13353
- Medizinische Klinik mit Schwerpunkt Haematologie und Onkologie, Charité-Universitaetsmedizin Berlin
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Gent, Bélgica, 9000
- Universitair Ziekenhuis Gent/Dienst Gastroenterologie
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Alberta
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Edmonton, Alberta, Canadá, T6G 1Z2
- Cross Cancer Institute
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Manitoba
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Winnipeg, Manitoba, Canadá, R3E 0V9
- CancerCare Manitoba
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Winnipeg, Manitoba, Canadá, R2H 2A6
- Cancer Care Manitoba
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Ontario
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Sault Ste Marie, Ontario, Canadá, P6A 2C4
- Sault Area Hospital
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Toronto, Ontario, Canadá, M5G 2M9
- Princess Margaret Hospital
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Quebec
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Montreal, Quebec, Canadá, H2X 3J4
- CHUM, Hopital Saint-Luc
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Barcelona, España, 08036
- Hospital Clinic i Provincial de Barcelona
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Barcelona, España, 08035
- Hospital Universitario Vall d´Hebron
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Sevilla, España, 41013
- Hospital Universitario Virgen Del Rocio
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California
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Antioch, California, Estados Unidos, 94509
- East Bay Medical Oncology/Hematology Medical Associates Inc.
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Berkeley, California, Estados Unidos, 94704
- Alta Bates Comprehensive Cancer Center
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Concord, California, Estados Unidos, 94520
- Bay Area Cancer Research Group
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Concord, California, Estados Unidos, 94520
- East Bay Medical Oncology/Hematology Medical Associates, Inc.
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Connecticut
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Stamford, Connecticut, Estados Unidos, 06902-3628
- Hematology Oncology, P.C.
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Florida
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Miami, Florida, Estados Unidos, 33136
- University of Miami Hospital & Clinics
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Miami, Florida, Estados Unidos, 33136
- Jackson Memorial Hospital & Clinics
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Tampa, Florida, Estados Unidos, 33612-9497
- H Lee Moffitt Cancer Center & Research Institute
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Maine
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Biddeford, Maine, Estados Unidos, 04005
- Maine Center for Cancer Medicine and Blood Disorders
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Brunswick, Maine, Estados Unidos, 04011
- Maine Center for Cancer Medicine and Blood Disorders
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Scarborough, Maine, Estados Unidos, 04074
- Maine Center for Cancer Medicine and Blood Disorders
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63141
- Arch Medical Services, Inc. d/b/a The Center for Cancer Care and Research
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Washington, Missouri, Estados Unidos, 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, Estados Unidos, 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, Estados Unidos, 27103
- Piedmont Hematology Oncology Association
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Winston-Salem, North Carolina, Estados Unidos, 27292
- Piedmont Hematology Oncology Associates
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Wisconsin
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Madison, Wisconsin, Estados Unidos, 53792
- University of Wisconsin Hospital and Clinics
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Marseille, Francia, 13005
- Hôpital La Timone
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Paris Cedex 13, Francia, 75651
- Hopital de la Pitie Salpetriere
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Toulouse, Francia, 31052
- Institut Claudius Regaud
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Saint Herblain Cedex
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Saint-Herblain, Saint Herblain Cedex, Francia, 44805
- Service Oncologie Medicale
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Milano, Italia, 20133
- Fondazione IRCCS, Istituto Nazionale Tumori, Oncologia Medica B
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Roma, Italia, 00168
- Unita Operativa, Oncologia Medica, Istituto di Medicina Interna e Geriatria
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Edinburgh, Reino Unido, EH4 2XU
- Western General Hospitals Nhs Trust
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London, Reino Unido, W12 OHS
- Hammersmith Hospital
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Hampshire
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Southampton, Hampshire, Reino Unido, SO16 6YD
- Cancer Research UK Clinical Centre
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Leicestershire
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Leicester, Leicestershire, Reino Unido, LE1 5WW
- Department of Cancer Studies & Molecular Medicine
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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)
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: Gemcitabina
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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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Experimental: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall Survival (OS)
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Dose Confirmation of Axitinib (AG-013736) on Basis of Number of Participants With Dose Limiting Toxicity (DLT)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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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).
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
5 de julio de 2005
Finalización primaria (Actual)
14 de marzo de 2008
Finalización del estudio (Actual)
14 de marzo de 2008
Fechas de registro del estudio
Enviado por primera vez
13 de septiembre de 2005
Primero enviado que cumplió con los criterios de control de calidad
13 de septiembre de 2005
Publicado por primera vez (Estimar)
22 de septiembre de 2005
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
14 de mayo de 2019
Última actualización enviada que cumplió con los criterios de control de calidad
22 de abril de 2019
Última verificación
1 de abril de 2019
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Neoplasias
- Neoplasias por sitio
- Enfermedades del sistema endocrino
- Neoplasias del Sistema Digestivo
- Neoplasias de glándulas endocrinas
- Enfermedades pancreáticas
- Neoplasias pancreáticas
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de enzimas
- Antimetabolitos, Antineoplásicos
- Antimetabolitos
- Agentes antineoplásicos
- Agentes inmunosupresores
- Factores inmunológicos
- Inhibidores de la proteína quinasa
- Gemcitabina
- Axitinib
Otros números de identificación del estudio
- A4061016
- 2005-000053-30 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan 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.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .