The BEACON Study (Breast Cancer Outcomes With NKTR-102)

Metastatic Breast Cancer Clinical Trial

— BEACON  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01492101
• Other study ID #: 11-PIR-11
• Status: Completed
• Phase: Phase 3
• Start date: December 2011
• Est. completion date: June 2016

Study information

• Verified date: May 2021
• Source: Nektar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 852
• Est. completion date: June 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Recurrent Breast Cancer
• Metastatic Breast Cancer

Intervention

Drug:
• NKTR-102
145 mg/m2 NKTR-102 will be delivered q21day as a 90-minute intravenous (IV) infusion on day 1 of each treatment cycle.
• Treatment of Physician's Choice (TPC)
One of the following Treatment of Physician Choice will be administered per standard of care: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Bruxelles
Belgium	GHdC - Site Notre Dame	Charleroi
Belgium	Universtair Ziekenhuis Antwerpen	Edegem
Belgium	UZ Gent Medische Oncologie	Gent
Belgium	UZ Leuven, Campus Gasthuisberg, trialbureau Algemene Medische Oncologie	Leuven
Belgium	Centre Hospitalier Universitaire de Liège- Site du Sart Tilman	Liège
Belgium	Centre Hospitalier Universitaire Ambroise Paré	Mons,
Belgium	GZA Ziekenhuizen, Campus St Augustinus, CLINICAL TRIALS ONCOLOGY	Wilrijk
Canada	CHUM-Hopital Notre-Dame	Montreal	Quebec
Canada	MUHC- Montreal General Hospital	Montreal	Quebec
Canada	Hôpital Charles-LeMoyne - CICM	Québec
Canada	Odette Cancer Centre OCC Clinical Research	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
France	Institut Bergonie Service Oncologie Médicale	Bordeaux
France	Sorecoh	Le Mans
France	Centre Oscar Lambret	Lille Cedex
France	Institut Paoli Calmettes, Service Pharmacie	Marseille
France	Centra Regional de Lutte contre le Cancer	Montpellier
France	Hopital Tenon Service oncologie médicale	Paris
France	Institut Curie, UGEC	Paris
France	Centre Régional de Lutte Contre le Cancer Nantes Atlantique René Gauducheau	Saint Herblain
France	Institut de Cancérologie Gustave Roussy	Villejuif
Germany	Klinikum St. Marien Amberg	Amberg
Germany	Onkoplus	Berlin
Germany	Oncoresearch	Dortmund
Germany	Universitaetsklinikum Erlangen	Erlangen
Germany	Wilhelm-Anton-Hospital gGmbH	Goch
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Ulm, Frauenklinik	Ulm
Italy	Istituto tumori Giovanni Paolo II-ospedale oncologico, Oncologia Medica e Sperimentale	Bari
Italy	Via Olgettina	Milano
Italy	Azienda Ospedaliero Universitaria Pisana, U.O. Oncologia Medica	Pisa
Italy	Oncologia Ospedale Infermi- Viale	Rimini
Italy	Istituto Nazionale tumori Regina Elena IRCCS	Roma
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Irwon-dong	Seoul
Korea, Republic of	Asan Medical Center	Seoul
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	Seoul National University Hospital,	Soeul
Korea, Republic of	Hematology-oncology Department, Ajou University Hospital	Sowon	Suwon
Netherlands	VUmc	Amsterdam
Netherlands	MUMC	Maastricht
Netherlands	Tweesteden Ziekenhuis	Tilburg
Russian Federation	Leningrad Regional Oncology Dispensary	Kuz'molovskiy
Russian Federation	State Institution "Russian Oncology Research Centre named after N.N. Blokhin RAMS"	Moscow
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov	Saint Petersburg
Russian Federation	Non-state Health Institution "Dorozhnaya Clinical Hospital of OAO "Russian Railways"	St. Petersburg
Russian Federation	St. Petersburg State Budget Healthcare Institution "City Clinical Oncology Dispensary"	St. Petersburg
Spain	Hospital Vall d'Hebron	Barcelona
Spain	ICO l´Hospitalet - Hospital Duran i Reynals	Barcelona
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Cancer Center Arturo	Madrid
Spain	Hospital Sant Joan de Reus	Tarragona
United Kingdom	Clinical Trials Unit, Velindre Cancer Centre	Cardiff
United Kingdom	Beaston Oncology Center	Glasgow
United Kingdom	St James University Hospital	Leeds
United Kingdom	NCRN	London
United Kingdom	The Christie Hospitals NHS Foundation Trust	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Cancer Clinical Trials Centre, Weston Park Hospital	Sheffield
United States	Texas Oncology-Abilene	Abilene	Texas
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	UNM Cancer Center	Albuquerque	New Mexico
United States	Northeast Georgia Cancer Care	Athens	Georgia
United States	Emory University	Atlanta	Georgia
United States	Peachtree Hematology Oncology Consultants	Atlanta	Georgia
United States	Texas Oncology-Austin Midtown	Austin	Texas
United States	Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center	Beaumont	Texas
United States	Texas Oncology-Bedford	Bedford	Texas
United States	Frontier Cancer Center and Blood Institute	Billings	Montana
United States	Monte fiore	Bronx	New York
United States	Sciode Medical Associates, PLLC, d.b.a. Eastchester Center for Cancer Care	Bronx	New York
United States	Providence Health System - Southern California d/b/a Roy and Patricia Disney Family Cancer Center	Burbank	California
United States	Hall-Perrine Cancer Center, 3rd Floor	Cedar Rapids	Iowa
United States	Carolinas Hematology Oncology Associates	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	The University of Chicago Medicine	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Maryland Oncology Hematology, P.A.	Columbia	Maryland
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Comprehensive Breast Cancer	Columbus	Ohio
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology-Dallas Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology-Medical City Dallas	Dallas	Texas
United States	Texas Oncology-Denton South	Denton	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	DUMC, Duke South	Durham	North Carolina
United States	Cancer Centers of the Carolinas	Easley	South Carolina
United States	Sanford Research/USD	Fargo	North Dakota
United States	Arizona Oncology Associates, PC - NAHOA	Flagstaff	Arizona
United States	Texas Oncology-Fort Worth	Fort Worth	Texas
United States	Cancer TEAM Bellin Health	Green Bay	Wisconsin
United States	Texas Oncology-Memorial City	Houston	Texas
United States	IU Health Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Medical Oncology Associates of Wyoming Valley, PC	Kingston	Pennsylvania
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Texas Oncology-Lewisville	Lewisville	Texas
United States	University of Southern California	Los Angeles	California
United States	Louisville Oncology Clinical Research Program	Louisville	Kentucky
United States	Central Georgia Cancer Care	Macon	Georgia
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	The West Clinic	Memphis	Tennessee
United States	Texas Oncology-Mesquite	Mesquite	Texas
United States	Advanced Medical Specialties	Miami	Florida
United States	University of Miami School of Medicine	Miami	Florida
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Texas Oncology-Midland Allison Cancer Center	Midland	Texas
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Hematology-Oncology Associates of Northern NJ, PA	Morristown	New Jersey
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Sarah Cannon Research Institute (SCRI)	Nashville	Tennessee
United States	The cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Beth Israel Medical Center	New York	New York
United States	Cornell University	New York	New York
United States	Oncology Specialists	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Kansas City Cancer Center	Overland Park	Kansas
United States	PMK Medical Group, Inc., DBA Ventura County Hematology Oncology Specialists	Oxnard	California
United States	Wilshire Oncology Medical Group, Inc.	Pasadena	California
United States	Illinois Cancer Care, P.C.	Peoria	Illinois
United States	Texas Oncology, P.A. - Plano	Plano	Texas
United States	Florida Cancer Research Institute	Plantation	Florida
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Northwest Cancer Specialists, P.C.	Portland	Oregon
United States	Desert Hematology Oncology Medical Group	Rancho Mirage	California
United States	Mayo Clinic	Rochester	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Salem	Virginia
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	University of California San Francisco	San Francisco	California
United States	Summit Cancer Care, P.C.	Savannah	Georgia
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Texas Oncology - Sherman	Sherman	Texas
United States	Sanford Research/USD	Sioux Falls	South Dakota
United States	Cancer Care Northwest	Spokane	Washington
United States	Stanford University School of Medicine	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Texas Oncology-Tyler	Tyler	Texas
United States	Kaiser Permanente	Vallejo	California
United States	Cooper University Hospital	Voorhees	New Jersey
United States	Medstar	Washington	District of Columbia
United States	Pre clinical Science Bldg LR3	Washington	District of Columbia
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Nektar Therapeutics

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population	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.	36 Months
Secondary	Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population	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.	Up to 38 months.
Secondary	Clinical Benefit Rate (CBR): ITT Population	CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (= 182 days).	Up to 38 months.
Secondary	Duration of Response (DOR): Efficacy Evaluable Population	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.	Up to 38 months.
Secondary	Incidence of Dose Reductions: Safety Population	Proportion of subjects who had a reduction in dose.	Up to 38 months.
Secondary	Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population	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.	Up to 39 months
Secondary	QLQ-C30 Individual Scale, Change Over Time: ITT Population	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.	From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.
Secondary	Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population	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.	Baseline
Secondary	BR23 Score Change Over Time: ITT Population	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.	Up to 38 months.
Secondary	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]	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.	Up to 38 months.
Secondary	Population Mean ± SD Maximum Plasma Concentration (Cmax) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [26]	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.	Up to 38 months.
Secondary	Population Mean ± SD Elimination Half-life (t½) for NKTR-102 After Multiple Administration of 145 mg/m^2 NKTR-102 [27]	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.	Up to 38 months.
Secondary	Objective Response Rate (ORR): Efficacy Evaluable Population	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.	Up to 38 months.