The BEACON Study (Breast Cancer Outcomes With NKTR-102)
- Conditions
- Metastatic Breast CancerLocally Recurrent Breast Cancer
- Interventions
- Drug: Treatment of Physician's Choice (TPC)
- Registration Number
- NCT01492101
- Lead Sponsor
- Nektar Therapeutics
- Brief Summary
The study is designed as an open-label, randomized, parallel, two arm, multicenter, international Phase 3 study in patients with recurrent or metastatic breast cancer previously treated with cytotoxic chemotherapy regimens.
The primary study objective is to compare overall survival of patients who receive NKTR-102 given once every 21 days to patients who receive treatment of Physician's Choice selected from a list of seven single-agent intravenous therapies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 852
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NKTR-102 NKTR-102 - Physician's Treatment of Choice Treatment of Physician's Choice (TPC) -
- Primary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population 36 Months Duration of OS was defined as the time from the date of randomisation to the date of death due to any cause. Subjects were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. OS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. Subjects who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Subjects who did not have any follow-up since the date of randomization were censored at the date of randomization.
- Secondary Outcome Measures
Name Time Method Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population Up to 38 months. PFS was defined as the time from the date of randomization to the earliest date of disease progression (assessed by the investigator according to RECIST version 1.1) or death due to any cause. PFS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. For subjects whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For subjects who received new anti-cancer therapy, the PFS time was censored at the start of the new anti-cancer therapy.
Clinical Benefit Rate (CBR): ITT Population Up to 38 months. CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (≥ 182 days).
Duration of Response (DOR): Efficacy Evaluable Population Up to 38 months. DOR was defined as the time from first documented CR or PR until the earliest evidence of disease progression or death from any cause. Subjects who were alive without documented disease progression per RECIST version 1.1 were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease.
Incidence of Dose Reductions: Safety Population Up to 38 months. Proportion of subjects who had a reduction in dose.
Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population Up to 39 months The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhoea, constipation, insomnia and dyspnoea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
QLQ-C30 Individual Scale, Change Over Time: ITT Population From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56. The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhea, constipation, insomnia and dyspnea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (from 1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population Baseline The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items to assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
BR23 Score Change Over Time: ITT Population Up to 38 months. The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
Objective Response Rate (ORR): Efficacy Evaluable Population Up to 38 months. ORR was defined as the proportion of subjects with a complete response (CR) or a partial response (PR), assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 The analyses were performed for subjects in the efficacy evaluable population who had measurable disease as determined by the investigator at baseline.
Population Mean ± Standard Deviation (SD) Area Under the Concentration-Time Curve (AUC) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [25] Up to 38 months. Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population pharmacokinetic (PK) model-derived mean AUC values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.
Population Mean ± SD Maximum Plasma Concentration (Cmax) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [26] Up to 38 months. Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean Cmax values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.
Population Mean ± SD Elimination Half-life (t½) for NKTR-102 After Multiple Administration of 145 mg/m^2 NKTR-102 [27] Up to 38 months. Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean t½ values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. The t½ of all analytes was primarily driven by NKTR-102. Thus, the NKTR-102 t½ of 37 days also applies to all NKTR-102 metabolites.
Trial Locations
- Locations (152)
Emory University
🇺🇸Atlanta, Georgia, United States
Odette Cancer Centre OCC Clinical Research
🇨🇦Toronto, Ontario, Canada
Universtair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Scientific Research Oncology Institute named after N.N. Petrov
🇷🇺Saint Petersburg, Russian Federation
Centre Hospitalier Universitaire de Liège- Site du Sart Tilman
🇧🇪Liège, Belgium
State Institution "Russian Oncology Research Centre named after N.N. Blokhin RAMS"
🇷🇺Moscow, Russian Federation
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
VUmc
🇳🇱Amsterdam, Netherlands
St. Petersburg State Budget Healthcare Institution "City Clinical Oncology Dispensary"
🇷🇺St. Petersburg, Russian Federation
Arizona Oncology Associates, PC - NAHOA
🇺🇸Flagstaff, Arizona, United States
PMK Medical Group, Inc., DBA Ventura County Hematology Oncology Specialists
🇺🇸Oxnard, California, United States
Providence Health System - Southern California d/b/a Roy and Patricia Disney Family Cancer Center
🇺🇸Burbank, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Wilshire Oncology Medical Group, Inc.
🇺🇸Pasadena, California, United States
Desert Hematology Oncology Medical Group
🇺🇸Rancho Mirage, California, United States
Stanford University School of Medicine
🇺🇸Stanford, California, United States
Pre clinical Science Bldg LR3
🇺🇸Washington, District of Columbia, United States
Kaiser Permanente
🇺🇸Vallejo, California, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Medstar
🇺🇸Washington, District of Columbia, United States
Florida Cancer Research Institute
🇺🇸Plantation, Florida, United States
University of Miami School of Medicine
🇺🇸Miami, Florida, United States
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
Northeast Georgia Cancer Care
🇺🇸Athens, Georgia, United States
Peachtree Hematology Oncology Consultants
🇺🇸Atlanta, Georgia, United States
The University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
Kansas City Cancer Center
🇺🇸Overland Park, Kansas, United States
IU Health Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Illinois Cancer Care, P.C.
🇺🇸Peoria, Illinois, United States
Hall-Perrine Cancer Center, 3rd Floor
🇺🇸Cedar Rapids, Iowa, United States
Louisville Oncology Clinical Research Program
🇺🇸Louisville, Kentucky, United States
Sciode Medical Associates, PLLC, d.b.a. Eastchester Center for Cancer Care
🇺🇸Bronx, New York, United States
The cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Cornell University
🇺🇸New York, New York, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Coborn Cancer Center
🇺🇸Saint Cloud, Minnesota, United States
Hematology-Oncology Associates of Northern NJ, PA
🇺🇸Morristown, New Jersey, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Cooper University Hospital
🇺🇸Voorhees, New Jersey, United States
Frontier Cancer Center and Blood Institute
🇺🇸Billings, Montana, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Texas Oncology-Medical City Dallas
🇺🇸Dallas, Texas, United States
Texas Oncology-Dallas Presbyterian Hospital
🇺🇸Dallas, Texas, United States
Comprehensive Breast Cancer
🇺🇸Columbus, Ohio, United States
Sanford Research/USD
🇺🇸Sioux Falls, South Dakota, United States
Signal Point Clinical Research Center
🇺🇸Middletown, Ohio, United States
Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
🇺🇸Salem, Virginia, United States
Carolinas Hematology Oncology Associates
🇺🇸Charlotte, North Carolina, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
Medical Oncology Associates of Wyoming Valley, PC
🇺🇸Kingston, Pennsylvania, United States
Cancer Centers of the Carolinas
🇺🇸Easley, South Carolina, United States
Texas Oncology-Bedford
🇺🇸Bedford, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology-Abilene
🇺🇸Abilene, Texas, United States
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center
🇺🇸Beaumont, Texas, United States
Texas Oncology-Fort Worth
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Sherman
🇺🇸Sherman, Texas, United States
Texas Oncology-Denton South
🇺🇸Denton, Texas, United States
Texas Oncology-Lewisville
🇺🇸Lewisville, Texas, United States
Texas Oncology-Memorial City
🇺🇸Houston, Texas, United States
Institut Jules Bordet
🇧🇪Bruxelles, Belgium
GHdC - Site Notre Dame
🇧🇪Charleroi, Belgium
Texas Oncology-Mesquite
🇺🇸Mesquite, Texas, United States
Texas Oncology-Midland Allison Cancer Center
🇺🇸Midland, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Cancer Care Northwest
🇺🇸Spokane, Washington, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Texas Oncology-Tyler
🇺🇸Tyler, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States
Sorecoh
🇫🇷Le Mans, France
UZ Leuven, Campus Gasthuisberg, trialbureau Algemene Medische Oncologie
🇧🇪Leuven, Belgium
Cancer TEAM Bellin Health
🇺🇸Green Bay, Wisconsin, United States
UZ Gent Medische Oncologie
🇧🇪Gent, Belgium
Centre Hospitalier Universitaire Ambroise Paré
🇧🇪Mons,, Belgium
GZA Ziekenhuizen, Campus St Augustinus, CLINICAL TRIALS ONCOLOGY
🇧🇪Wilrijk, Belgium
British Columbia Cancer Agency
🇨🇦Vancouver, British Columbia, Canada
MUHC- Montreal General Hospital
🇨🇦Montreal, Quebec, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Institut Bergonie Service Oncologie Médicale
🇫🇷Bordeaux, France
Hôpital Charles-LeMoyne - CICM
🇨🇦Québec, Canada
CHUM-Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
Centra Regional de Lutte contre le Cancer
🇫🇷Montpellier, France
Wilhelm-Anton-Hospital gGmbH
🇩🇪Goch, Germany
Universitaetsklinikum Ulm, Frauenklinik
🇩🇪Ulm, Germany
Via Olgettina
🇮🇹Milano, Italy
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
MUMC
🇳🇱Maastricht, Netherlands
Seoul National University Hospital,
🇰🇷Soeul, Korea, Republic of
Leningrad Regional Oncology Dispensary
🇷🇺Kuz'molovskiy, Russian Federation
Beaston Oncology Center
🇬🇧Glasgow, United Kingdom
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Clinical Trials Unit, Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Azienda Ospedaliero Universitaria Pisana, U.O. Oncologia Medica
🇮🇹Pisa, Italy
Centre Oscar Lambret
🇫🇷Lille Cedex, France
Institut Paoli Calmettes, Service Pharmacie
🇫🇷Marseille, France
Institut Curie, UGEC
🇫🇷Paris, France
Hopital Tenon Service oncologie médicale
🇫🇷Paris, France
Beth Israel Medical Center
🇺🇸New York, New York, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
DUMC, Duke South
🇺🇸Durham, North Carolina, United States
Northwest Cancer Specialists, P.C.
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute (SCRI)
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Cancer Care Centers of South Texas
🇺🇸San Antonio, Texas, United States
Texas Oncology, P.A. - Plano
🇺🇸Plano, Texas, United States
Hematology Oncology Associates of the Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Central Georgia Cancer Care
🇺🇸Macon, Georgia, United States
Northwest Georgia Oncology Centers, P.C.
🇺🇸Marietta, Georgia, United States
UNM Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Summit Cancer Care, P.C.
🇺🇸Savannah, Georgia, United States
Oncology Specialists
🇺🇸Niles, Illinois, United States
Maryland Oncology Hematology, P.A.
🇺🇸Columbia, Maryland, United States
Monte fiore
🇺🇸Bronx, New York, United States
Centre Régional de Lutte Contre le Cancer Nantes Atlantique René Gauducheau
🇫🇷Saint Herblain, France
Onkoplus
🇩🇪Berlin, Germany
Klinikum St. Marien Amberg
🇩🇪Amberg, Germany
Institut de Cancérologie Gustave Roussy
🇫🇷Villejuif, France
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Oncoresearch
🇩🇪Dortmund, Germany
Universitaetsklinikum Erlangen
🇩🇪Erlangen, Germany
Istituto tumori Giovanni Paolo II-ospedale oncologico, Oncologia Medica e Sperimentale
🇮🇹Bari, Italy
Oncologia Ospedale Infermi- Viale
🇮🇹Rimini, Italy
Istituto Nazionale tumori Regina Elena IRCCS
🇮🇹Roma, Italy
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungcheongbuk-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Irwon-dong, Seoul, Korea, Republic of
Hematology-oncology Department, Ajou University Hospital
🇰🇷Sŏwŏn, Suwon, Korea, Republic of
Hematology-oncology Department, Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Tweesteden Ziekenhuis
🇳🇱Tilburg, Netherlands
Non-state Health Institution "Dorozhnaya Clinical Hospital of OAO "Russian Railways"
🇷🇺St. Petersburg, Russian Federation
ICO l´Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
MD Anderson Cancer Center Arturo
🇪🇸Madrid, Spain
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Sant Joan de Reus
🇪🇸Tarragona, Spain
St James University Hospital
🇬🇧Leeds, United Kingdom
The Christie Hospitals NHS Foundation Trust
🇬🇧Manchester, United Kingdom
NCRN
🇬🇧London, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Cancer Clinical Trials Centre, Weston Park Hospital
🇬🇧Sheffield, United Kingdom
University of Virginia
🇺🇸Charlottesville, Virginia, United States