Clinical trial NCT01492101: The BEACON Study (Breast Cancer Outcomes With NKTR-102)
Official title: The BEACON Study (Breast Cancer Outcomes With NKTR-102): A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 Versus Treatment of Physician's Choice (TPC) in Patients With Locally Recurrent or Metastatic Breast Cancer Previously Treated With an Anthracycline, a Taxane and Capecitabine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Locally Recurrent Breast Cancer
Metastatic Breast Cancer
Lead sponsor: Nektar Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-12-14
Enrollment: 852
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria (major highlights):

* Patient is an adult female with histologically or cytologically confirmed carcinoma of the breast for whom single-agent cytotoxic chemotherapy is indicated
* Patient can have either measurable or non-measurable disease by RECIST.
* Patient has received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, a taxane and capecitabine
* Patient has minimum of 2 and a maximum of 5 prior cytotoxic chemotherapy regimens with the last dose administered within 6 months. A minimum of two chemotherapy regimens had to be for locally recurrent and/or metastatic disease. All therapy received prior to a diagnosis of metastatic disease (eg, neoadjuvant, adjuvant or repeated adjuvant therapy following a second resection) is counted as one regimen.
* Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate hematopoietic, liver and kidney functions.

Exclusion Criteria (major highlights):

* Patient with chemotherapy within 21 days, radiotherapy within 14 days, biological therapy with 14 days, hormonal therapy within 7 days and investigational therapy within 21 days prior to randomization.
* Patient with any major surgery within 28 days prior to randomization.
* Patient with concurrent use of biologic agents for the treatment of cancer including antibodies or any investigational agent(s).
* Patient with prior treatment for cancer with a camptothecin derivative.
* Patient with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care to control diarrhea in the 28 days prior to randomization.
* Patient received pharmacotherapy for hepatitis B or C, tuberculosis or HIV.
* Patient with known cirrhosis diagnosed with Child-PUGH Class A or higher liver disease.
* Patient with prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization.
* Patient requiring daily use of oxygen supplementation in the 28 days prior to randomization.
* Patients with significant cardiovascular impairment.

Primary outcomes:
measure: Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population
timeFrame: 36 Months
Secondary outcomes:
measure: Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population
timeFrame: Up to 38 months.
measure: Clinical Benefit Rate (CBR): ITT Population
timeFrame: Up to 38 months.
measure: Duration of Response (DOR): Efficacy Evaluable Population
timeFrame: Up to 38 months.
measure: Incidence of Dose Reductions: Safety Population
timeFrame: Up to 38 months.
measure: Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population
timeFrame: Up to 39 months
measure: QLQ-C30 Individual Scale, Change Over Time: ITT Population
timeFrame: From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.
measure: Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population
timeFrame: Baseline
measure: BR23 Score Change Over Time: ITT Population
timeFrame: Up to 38 months.
measure: 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]
timeFrame: Up to 38 months.
measure: Population Mean ± SD Maximum Plasma Concentration (Cmax) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [26]
timeFrame: Up to 38 months.
measure: Population Mean ± SD Elimination Half-life (t½) for NKTR-102 After Multiple Administration of 145 mg/m^2 NKTR-102 [27]
timeFrame: Up to 38 months.
measure: Objective Response Rate (ORR): Efficacy Evaluable Population
timeFrame: Up to 38 months.
Other outcomes:
Locations:
city: Flagstaff
country: United States
facility: Arizona Oncology Associates, PC - NAHOA
state: Arizona
city: Burbank
country: United States
facility: Providence Health System - Southern California d/b/a Roy and Patricia Disney Family Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Oxnard
country: United States
facility: PMK Medical Group, Inc., DBA Ventura County Hematology Oncology Specialists
state: California
city: Pasadena
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Washington
country: United States
facility: Pre clinical Science Bldg LR3
state: District of Columbia
city: Washington
country: United States
facility: Medstar
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: Plantation
country: United States
facility: Florida Cancer Research Institute
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology Oncology Associates of the Treasure Coast
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care
state: Georgia
city: Atlanta
country: United States
facility: Peachtree Hematology Oncology Consultants
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Macon
country: United States
facility: Central Georgia Cancer Care
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, P.C.
state: Georgia
city: Savannah
country: United States
facility: Summit Cancer Care, P.C.
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: Niles
country: United States
facility: Oncology Specialists
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care, P.C.
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Simon Cancer Center
state: Indiana
city: Cedar Rapids
country: United States
facility: Hall-Perrine Cancer Center, 3rd Floor
state: Iowa
city: Overland Park
country: United States
facility: Kansas City Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Louisville Oncology Clinical Research Program
state: Kentucky
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Billings
country: United States
facility: Frontier Cancer Center and Blood Institute
state: Montana
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Morristown
country: United States
facility: Hematology-Oncology Associates of Northern NJ, PA
state: New Jersey
city: New Brunswick
country: United States
facility: The cancer Institute of New Jersey
state: New Jersey
city: Voorhees
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: UNM Cancer Center
state: New Mexico
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Bronx
country: United States
facility: Monte fiore
state: New York
city: Bronx
country: United States
facility: Sciode Medical Associates, PLLC, d.b.a. Eastchester Center for Cancer Care
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Cornell University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Hematology Oncology Associates
state: North Carolina
city: Durham
country: United States
facility: DUMC, Duke South
state: North Carolina
city: Fargo
country: United States
facility: Sanford Research/USD
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Comprehensive Breast Cancer
state: Ohio
city: Middletown
country: United States
facility: Signal Point Clinical Research Center
state: Ohio
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Kingston
country: United States
facility: Medical Oncology Associates of Wyoming Valley, PC
state: Pennsylvania
city: Easley
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Research/USD
state: South Dakota
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI)
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Abilene
country: United States
facility: Texas Oncology-Abilene
state: Texas
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology-Bedford
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Dallas Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Denton
country: United States
facility: Texas Oncology-Denton South
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Memorial City
state: Texas
city: Lewisville
country: United States
facility: Texas Oncology-Lewisville
state: Texas
city: Mesquite
country: United States
facility: Texas Oncology-Mesquite
state: Texas
city: Midland
country: United States
facility: Texas Oncology-Midland Allison Cancer Center
state: Texas
city: Plano
country: United States
facility: Texas Oncology, P.A. - Plano
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Sherman
country: United States
facility: Texas Oncology - Sherman
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
city: Green Bay
country: United States
facility: Cancer TEAM Bellin Health
state: Wisconsin
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Charleroi
country: Belgium
facility: GHdC - Site Notre Dame
city: Edegem
country: Belgium
facility: Universtair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: UZ Gent Medische Oncologie
city: Leuven
country: Belgium
facility: UZ Leuven, Campus Gasthuisberg, trialbureau Algemene Medische Oncologie
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liège- Site du Sart Tilman
city: Mons,
country: Belgium
facility: Centre Hospitalier Universitaire Ambroise Paré
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen, Campus St Augustinus, CLINICAL TRIALS ONCOLOGY
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Toronto
country: Canada
facility: Odette Cancer Centre OCC Clinical Research
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: MUHC- Montreal General Hospital
state: Quebec
city: Québec
country: Canada
facility: Hôpital Charles-LeMoyne - CICM
city: Bordeaux
country: France
facility: Institut Bergonie Service Oncologie Médicale
city: Le Mans
country: France
facility: Sorecoh
city: Lille Cedex
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut Paoli Calmettes, Service Pharmacie
city: Montpellier
country: France
facility: Centra Regional de Lutte contre le Cancer
city: Paris
country: France
facility: Institut Curie, UGEC
city: Paris
country: France
facility: Hopital Tenon Service oncologie médicale
city: Saint Herblain
country: France
facility: Centre Régional de Lutte Contre le Cancer Nantes Atlantique René Gauducheau
city: Villejuif
country: France
facility: Institut de Cancérologie Gustave Roussy
city: Amberg
country: Germany
facility: Klinikum St. Marien Amberg
city: Berlin
country: Germany
facility: Onkoplus
city: Dortmund
country: Germany
facility: Oncoresearch
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Goch
country: Germany
facility: Wilhelm-Anton-Hospital gGmbH
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm, Frauenklinik
city: Bari
country: Italy
facility: Istituto tumori Giovanni Paolo II-ospedale oncologico, Oncologia Medica e Sperimentale
city: Milano
country: Italy
facility: Via Olgettina
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana, U.O. Oncologia Medica
city: Rimini
country: Italy
facility: Oncologia Ospedale Infermi- Viale
city: Roma
country: Italy
facility: Istituto Nazionale tumori Regina Elena IRCCS
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-do
city: Irwon-dong
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Sŏwŏn
country: Korea, Republic of
facility: Hematology-oncology Department, Ajou University Hospital
state: Suwon
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Hematology-oncology Department, Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Soeul
country: Korea, Republic of
facility: Seoul National University Hospital,
city: Amsterdam
country: Netherlands
facility: VUmc
city: Maastricht
country: Netherlands
facility: MUMC
city: Tilburg
country: Netherlands
facility: Tweesteden Ziekenhuis
city: Kuz'molovskiy
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: State Institution "Russian Oncology Research Centre named after N.N. Blokhin RAMS"
city: Saint Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute named after N.N. Petrov
city: St. Petersburg
country: Russian Federation
facility: Non-state Health Institution "Dorozhnaya Clinical Hospital of OAO "Russian Railways"
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Budget Healthcare Institution "City Clinical Oncology Dispensary"
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Arturo
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Tarragona
country: Spain
facility: Hospital Sant Joan de Reus
city: Cardiff
country: United Kingdom
facility: Clinical Trials Unit, Velindre Cancer Centre
city: Glasgow
country: United Kingdom
facility: Beaston Oncology Center
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: NCRN
city: Manchester
country: United Kingdom
facility: The Christie Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Sheffield
country: United Kingdom
facility: Cancer Clinical Trials Centre, Weston Park Hospital
Study officials:
affiliation: Nektar Therapeutics
name: Alison Hannah, MD
role: STUDY_DIRECTOR
References:
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citation: Cortes J, Rugo HS, Awada A, Twelves C, Perez EA, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, O'Shaughnessy J. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017 Sep;165(2):329-341. doi: 10.1007/s10549-017-4304-7. Epub 2017 Jun 13.
citation: Twelves C, Cortes J, O'Shaughnessy J, Awada A, Perez EA, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Rugo HS. Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician's choice: Results from the randomised phase III BEACON trial. Eur J Cancer. 2017 May;76:205-215. doi: 10.1016/j.ejca.2017.02.011. Epub 2017 Mar 27.
citation: Perez EA, Awada A, O'Shaughnessy J, Rugo HS, Twelves C, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Cortes J. Etirinotecan pegol (NKTR-102) versus treatment of physician's choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1556-1568. doi: 10.1016/S1470-2045(15)00332-0. Epub 2015 Oct 22.