Tesetaxel Plus Reduced Dose of Capecitabine vs. Capecitabine in HER2 Negative, HR Positive, LA/MBC (CONTESSA)

A Multinational, Multicenter, Randomized, Phase 3 Study of Tesetaxel Plus a Reduced Dose of Capecitabine Versus Capecitabine Alone in Patients With HER2 Negative, HR Positive, Locally Advanced or Metastatic Breast Cancer Previously Treated With a Taxane

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel in patients with HER2 negative, HR positive LA/MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. The primary objective of the study is to compare the efficacy of tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone based on progression-free survival (PFS) as assessed by the Independent Radiologic Review Committee (IRC). 685 patients were enrolled.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tesetaxel and Capecitabine; Drug: Capecitabine

Detailed Description

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone in patients with HER2 negative, HR positive locally advanced or metastatic breast cancer (LA/MBC) previously treated with a taxane in the neoadjuvant or adjuvant setting. 685 patients were enrolled, including 674 who received treatment.

Patients randomly assigned to Arm A (tesetaxel plus a reduced dose of capecitabine) are administered:

• Tesetaxel (27 mg/m2) orally once every 21 days on Day 1 of each 21-day cycle; and
• Capecitabine (825 mg/m2) orally twice daily (in the morning and evening after a meal, for a total daily dose of 1,650 mg/m2) beginning with the evening dose on Day 1 through the morning dose on Day 15 of each 21-day cycle.

Patients randomly assigned to Arm B (approved dose of capecitabine alone) are administered:

• Capecitabine (1,250 mg/m2) orally twice daily (in the morning and evening after a meal, for a total daily dose of 2,500 mg/m2) beginning with the evening dose on Day 1 through the morning dose on Day 15 of each 21-day cycle

Dose modifications for tesetaxel and/or capecitabine are described in the study protocol.

Patients are treated until documentation of progressive disease (PD), evidence of unacceptable toxicity or other decision to discontinue treatment. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. The primary efficacy endpoint is PFS as assessed by the IRC. The secondary efficacy endpoints are overall survival (OS), objective response rate (ORR) as assessed by the IRC and disease control rate (DCR) as assessed by the IRC.

• Study Type: Interventional
• Enrollment (Actual): 685
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia
    • Flinders Medical Centre
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Border Medical Oncology
    • Wahroonga, New South Wales, Australia, 2076
      • Sydney Adventist Hospital
  • Queensland
    • South Brisbane, Queensland, Australia
      • Mater Cancer Care Centre
    • Woolloongabba, Queensland, Australia
      • Princess Alexandra Hospital
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Medical Centre
    • Frankston, Victoria, Australia, 3199
      • Peninsula and South Eastern Haematology and Oncology Group
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Breast Cancer Research Centre
    • Perth, Western Australia, Australia
      • St. John of God Subiaco Hospital
• Austria
  • Salzburg, Austria
    • Universitätsklinik Onkologie Landeskkrankenhaus
  • Schwaz, Austria
    • Facharzt für Frauenheilkunde und Geburtshilfe Spezialist für Brustchirurgie und Brustkrebs
  • Vienna, Austria
    • AKH-Frauenheilkunde
  • Wien, Austria, 1130
    • Ludwig Boltzmann Institut fur Klinische Onkologie und Photodynamische Therapie
• Belgium
  • Antwerp, Belgium, 02930
    • AZ Klina AUGUSTIJNSLEI
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Edegem, Belgium, 2900
    • UZA
  • Leuven, Belgium
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHC-Sant Joseph Oncology-Hematology
• Canada
  • Québec, Canada, G1S 4L8
    • CHU de Quebec-University Laval
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre - Nova Scotia Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montréal, Quebec, Canada, H1T 4B3
      • Hôpital Maisonneuve-Rosemont
    • Montréal, Quebec, Canada, H2X 3E4
      • Center Hospitalier de Montreal CHUM McPeak Sirois
    • Montréal, Quebec, Canada, H3T IE2
      • CIUSSS de Centre-Ouest-de-l'Île-de-Montréal Jewish General Hospital
    • Montréal, Quebec, Canada, H4J 3J1
      • McGill University Health Center
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke CIUSSS de lEstrie CHUS patyre
• Czechia
  • Hořovice, Czechia
    • NH Hospital a.s. Nemocnice Hořovice Onkologie
  • Olomouc, Czechia, 779 00
    • Onkologicka klinika FN Olomouc
  • Praha, Czechia, 128 08
    • Onkologicka Klinika (Vseobecna Fakultni Nemocnici v Praze )
  • Praha, Czechia, 150 06
    • Onkologicka Klinika (Fakultni Nemocnice v Motole)
• France
  • Besançon, France
    • CHRU J. Minjoz Service Oncologie
  • Caen, France, 14076
    • Centre François Baclesse Service the Recherche Clinique
  • Pierre-Benite, France, 69310
    • Hospices Civils de Lyon Sud Oncologie Medicale
  • Rennes, France, 44229
    • Centre Eugène Marquis
  • Saint-Cloud, France, 92210
    • Institut Curie - Hôpital René Huguenin
  • Strasbourg, France, 67085
    • Clinique Sainte Anne - Strasbourg Oncologie Libérale
  • Tours, France, 37044
    • Centre Hospitalier Regional et Universitaire de Tours CHRU
• Germany
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Berlin, Germany, 12203
    • Charité Universitätsmedizin Berlin-Campus Benjamin Franklin Klinik für Hämatologie, Onkologie und Tumorimmunologie
  • Hamburg, Germany, 20357
    • Mammazentrum HH am Krankenhaus Jerusalem
  • Kiel, Germany, 24015
    • UKSH, Campus Kiel Klinik für Gynäkologie und Geburtshilfe
  • Lueneburg, Germany, 21339
    • Staedtisches Klinikum Lueneburg gGmbH Brustzentrum und gynaekologisches Krebszentrum der Frauenklinik
  • München, Germany, 80366
    • LMU Klinikum der Universität München Breast Cancer
  • München, Germany, 81675
    • Technische Universität München Klinikum rechts der Isar Klinik und Poliklinik für Frauenheilkunde
  • Berlin
    • Erlangen, Berlin, Germany, 91054
      • Arzt der Studienzentrale Universitätsklinikum Erlangen
  • NRW
    • Köln, NRW, Germany, 50935
      • St. Elisabeth-Krankenhaus GmbH
  • Rhineland-Palatinate
    • Koblenz, Rhineland-Palatinate, Germany, 56068
      • InVO - Institut für Versorgungsforschung
    • Witten, Rhineland-Palatinate, Germany, 58452
      • St. Elisabethgruppe GmbH Marien Hospital Witten Brustzentrum
• Hungary
  • Budapest, Hungary
    • Semmelweis University
  • Budapest, Hungary
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary
    • Uzsoki Utcai Kórház
  • Budapest, Hungary
    • Military Hospital State Health Center
  • Nyíregyháza, Hungary
    • Szabolcs Szatmar Bereg Megyei Korhazak Es Egyetemi Oktatokorhaz
  • Pécs, Hungary, 7624
    • University of Pecs Department of Oncotherapy
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele - Medical Oncology Dept.
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia (IEO)
  • Modena, Italy, 41122
    • Centro Oncologico Modenese
  • Terni, Italy, 05100
    • S.C. Oncologia/Az. Osp.Ra. S Maria Terni
• Korea, Republic of
  • Busan, Korea, Republic of
    • Dong-A University Hospital
  • Daegu, Korea, Republic of
    • Kyungpook National University Hospital
  • Goyang, Korea, Republic of
    • National Cancer Center
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
  • Suwon, Korea, Republic of
    • Ajou University Hospital
  • Suwon, Korea, Republic of
    • St. Vincents Hospital
• Poland
  • Gdynia, Poland
    • Szpitale Pomorskie Oddział Onkologii i Radioterapii Powstania
  • Olsztyn, Poland, 10-357
    • Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc, Oddzial Onkologii z Pododdzialem Chemoioterapii
  • Rzeszów, Poland, 35-021
    • Mrukmed
  • Warsaw, Poland
    • Wilmed
  • Warszawa, Poland, 02-781
    • Klinika Nowotworów Piersi i Chirurgii Rekonstrukcyjnej Centrum Onkologii-Instytut
  • Żory, Poland
    • Onko-Dent G.L.Slomian
• Russian Federation
  • Saint Petersburg, Russian Federation, 198255
    • State Oncology Clinical Dispansery
  • Saint Petersburg, Russian Federation
    • Federal State Budgetary Institution Research Institute of Oncology named after N.N. Petrov of the Ministry of Health of the Russian Federation
• Singapore
  • Singapore, Singapore
    • National University Hospital
  • Singapore, Singapore
    • National Cancer Centre Singapore
  • Singapore, Singapore
    • John Hopkins Singapore International Medical Centre
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera Materno-Infantil (CHUAC)
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08023
    • Hospital Quirónsalud Barcelona
  • Barcelona, Spain, 08908
    • Institut Catala D'oncologia
  • Cáceres, Spain, 10003
    • HU San Pedro de Alcantara
  • La Coruña, Spain, 15009
    • Centro Oncologico de Galicia
  • Madrid, Spain, 28040
    • Fundación Jiménez Díaz
  • Madrid, Spain, 28040
    • Hospital Clínico San Carlos
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal Servicio de Oncologia
  • Madrid, Spain, 28034
    • IOB_Hospital Ruber Internacional
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen De La Victoria
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet Paseo Isabel la Catolica 1-3 Edificio de Maternidad
  • Gipuzkoa
    • San Sebastián, Gipuzkoa, Spain
      • Onkologikoa
  • Manresa
    • Barcelona, Manresa, Spain, 08243
      • Althaia Hospital Sant Joan de Deu
• Taiwan
  • Taichung, Taiwan
    • Changhua Christian Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Tainan City, Taiwan
    • Chi Mei Medical Center
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Koo Foundation Sun Yat-Sen Cancer Center
  • Taipei City, Taiwan
    • National Taiwan University Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital Linkou Branch
• Thailand
  • Bangkok, Thailand
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand
    • Chulabhorn Hospital
  • Phitsanulok, Thailand
    • Buddhachinaraj Hospital
• Ukraine
  • Dnipro, Ukraine, 49102
    • Dnipropetrovsk City Multifield Clinical Hospital #4
  • Kharkiv, Ukraine, 61070
    • Communal Non-Profit Enterprise "Regional Center of Oncology"
  • Kryvyi Rih, Ukraine, 50048
    • Kryviy Rih Onkology Dispensary
  • Kyiv, Ukraine, 03022
    • National Cancer Institute
  • Lviv, Ukraine, 79031
    • Municipal Institution of Lviv Regional Council - Lviv Oncology Regional Treatment Diagnostic Center
  • Vinnytsia, Ukraine, 21029
    • Podilskiy Regional Center of Oncology
  • Zaporizhzhia, Ukraine, 69040
    • Communal Institution "Zaporizhzhia Regional Clinical Oncological Dispensary"
  • Úzhgorod, Ukraine, 88000
    • Central City Clinical Hospital, City Oncology Center
• United Kingdom
  • Hertford, United Kingdom, SG14 1LP
    • Hertford County Hospital
  • London, United Kingdom, SE1 9RT
    • Cancer Centre, Guy's Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals Nhs Trust
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital Oncology Trials, Sunrise Centre
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers
    • Goodyear, Arizona, United States, 85338
      • Cancer Treatment Centers of America - Western Regional Medical Center
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates, P.C. - HOPE
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Genesis Cancer Center
    • Little Rock, Arkansas, United States, 72205
      • CARTI Cancer Center
  • California
    • Anaheim, California, United States, 92801-1824
      • Pacific Cancer Medical Center
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc.
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Healthcare
    • Los Angeles, California, United States, 90024
      • UCLA Medical Center
    • Redondo Beach, California, United States, 90277
      • Cancer Care - Torrance Memorial Physician Network
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • San Francisco, California, United States, 94115
      • University of California San Francisco - Helen Diller Family Comprehensive Cancer Center
    • San Luis Obispo, California, United States, 93401
      • San Luis Obispo Oncology & Hematology Health Center
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence
    • Santa Ana, California, United States, 92705
      • Cancer Research Collaboration and Breast Link
    • Stanford, California, United States, 94304
      • Stanford Cancer Center / Cancer Clinical Trials
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Center
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Western Connecticut Health Network
    • Hartford, Connecticut, United States, 06106
      • Hartford HealthCare
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Sarah Cannon Research Institute - Florida Cancer Specialists
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists of North Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Ocala, Florida, United States, 34471
      • Florida Cancer Affiliates - Ocala
    • Orlando, Florida, United States, 32806
      • Orlando Health
    • Plantation, Florida, United States, 33324
      • University of Miami Sylvester Comprehensive Cancer Center / Sylvester at Plantation
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists and Research Institute
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists and Research Institute - Panhandle Region
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists and Research Institute
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center
    • Newnan, Georgia, United States, 30265
      • Cancer Treatment Centers of America
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center - Duchossois Center for Advanced Medicine (DCAM)
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • American Health Network
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Maine
    • Biddeford, Maine, United States, 04005
      • SMHC Cancer Care and Blood Disorders
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland - Greenebaum Comprehensive Cancer Center
    • Baltimore, Maryland, United States, 21204
      • GBMC Cancer Center
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Health Care Center/ RCCA
    • Frederick, Maryland, United States, 21702
      • James M. Stockman Cancer Institute
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology, P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute, Allina Health
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Forrest General Cancer Center/Hattiesburg Clinic
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates
  • Missouri
    • Joplin, Missouri, United States, 64804
      • Mercy Cancer Center
    • Kansas City, Missouri, United States, 64131
      • HCA Midwest Health
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital St. Louis, David C. Pratt Cancer Center
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Frontier Cancer Center
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • Oncology Hematology West, P.C. dba Nebraska Cancer Specialists
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • New Jersey Hematology Oncology Associates
    • East Brunswick, New Jersey, United States, 08816
      • Regional Cancer Care Associates
    • Ridgewood, New Jersey, United States, 07451
      • The Valley Hospital
    • Sparta, New Jersey, United States, 07871
      • Regional Cancer Care Associates, LLC-Sparta
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Care Alliance - Southwest Gynecology Oncology
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, P.C.
    • East Setauket, New York, United States, 11733
      • New York Cancer and Blood Specialists
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York, P.C.
    • Johnson City, New York, United States, 13790
      • Broome Oncology, LLC
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Lineberger Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Ohio State University Comprehensive Cancer Center, Stephanie Spielman Comprehensive Breast Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Clinic Oncology and Hematology
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Philadelphia, Pennsylvania, United States, 19124
      • Cancer Treatment Centers of America - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15601
      • Magee-Women's Hospital of UPMC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute at Tennessee Oncology
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology - Bedford
    • Dallas, Texas, United States, 75231
      • Texas Oncology - Dallas Presbyterian Hospital
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75230
      • Texas Oncology - Medical City Dallas
    • Houston, Texas, United States, 77030
      • Oncology Consultants
    • Houston, Texas, United States, 77024
      • Texas Oncology - Memorial City
    • Houston, Texas, United States, 77024
      • Westside Surgical Hospital and Breast Center
    • Tyler, Texas, United States, 75701
      • HOPE Cancer Center of East Texas
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Bon Secours St. Francis
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Richmond, Virginia, United States, 23226
      • Virginia Cancer Institute
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Medical Center
    • Kennewick, Washington, United States, 99336
      • Kadlec Regional Medical Center
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Center
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female or male patients at least 18 years of age
2. Histologically or cytologically confirmed breast cancer
3. HER2 negative disease based on local testing: American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines should be utilized for assessing HER2 status
4. HR (estrogen receptor [ER] and/or progesterone receptor [PgR]) positive disease based on local testing: ASCO/CAP guidelines should be utilized for assessing HR status

5. Measurable disease per RECIST 1.1 or bone-only disease with lytic component

   • Patients with bone-only metastatic cancer must have a lytic or mixed lytic-blastic lesion that can be accurately assessed by computerized tomography (CT) or magnetic resonance imaging (MRI). Patients with bone-only disease without a lytic component (ie, blastic-only metastasis) are not eligible.

   • Known metastases to the CNS are permitted but not required. The following criteria apply:

     • Patients must be neurologically stable and either off corticosteroids or currently treated with a maximum daily dose of 4 mg of dexamethasone (or equivalent), with no increase in corticosteroid dose within 7 days prior to randomization
     • Patients with a history of CNS metastases but with no current evidence of CNS lesions following local therapy are eligible
     • Patients may have CNS metastases that are stable or progressing radiologically
     • Patients with current evidence of leptomeningeal disease are not eligible
     • Patients may have untreated brain metastases or previously treated brain metastases, as long as no immediate local CNS-directed therapy is indicated
     • Any prior whole brain radiation therapy must have been completed > 14 days prior to the date of randomization
     • Prior stereotactic brain radiosurgery is permitted
     • CNS surgical resection must have been completed > 28 days prior to the date of randomization; patient must have complete recovery from surgery
6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
7. Prior therapy (at least one completed dose) with a taxane-containing regimen in the neoadjuvant or adjuvant setting
8. Prior therapy with an anthracycline-containing regimen in the neoadjuvant, adjuvant, or metastatic setting, where indicated by local regulation or Investigator judgment.
9. Prior endocrine therapy with or without a CDK 4/6 inhibitor unless endocrine therapy is not indicated (ie, short relapse-free interval while on adjuvant endocrine therapy [endocrine resistance]; rapidly progressing disease/visceral crisis; or endocrine intolerance). Any targeted therapies approved for HER2 negative, HR positive LA/MBC, including everolimus, are permitted as prior therapy. There is no limit to the number of prior endocrine therapies.
10. Documented disease recurrence or disease progression of: (a) locally advanced disease that is not considered curable by surgery and/or radiation; or (b) metastatic disease.

11. Adequate hematologic, hepatic and renal function, as evidenced by:

    • Absolute neutrophil count (ANC) ≥ 1,500/μL without colony-stimulating factor support
    • Platelet count ≥ 100,000/μL
    • Hemoglobin ≥ 10 g/dL without need for hematopoietic growth factor or transfusion support
    • Total bilirubin < 1.5 × upper limit of normal (ULN); does not apply to patients with Gilbert's syndrome
    • Alanine aminotransferase (ALT) < 3 × ULN unless hepatic metastases are present, then < 5 × ULN
    • Aspartate aminotransferase (AST) < 3 × ULN unless hepatic metastases are present, then < 5 × ULN
    • Alkaline phosphatase < 2.5 × ULN unless hepatic metastases are present, then < 5 × ULN
    • Calculated creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula or local standard)
    • Serum albumin ≥ 3.0 g/dL
    • Prothrombin time (PT) < 1.5 × ULN or international normalized ratio (INR) < 1.3, and partial thromboplastin time (PTT) < 1.5 × ULN, unless the patient is on a therapeutic anticoagulant
12. Complete recovery to baseline or Grade 1 per National Cancer Institute (NCI) CTCAE version 5.0 from adverse effects of prior surgery, radiotherapy, endocrine therapy and other therapy, as applicable, with the exception of Grade 2 alopecia from prior chemotherapy
13. Ability to swallow an oral solid-dosage form of medication
14. A negative serum pregnancy test within 7 days prior to the first dose of Study treatment in women of childbearing potential (ie, all women except those who are post menopause for ≥ 1 year or who have a history of hysterectomy or surgical sterilization)

15. Women of childbearing potential must use an effective, non-hormonal form of contraception from Screening throughout the Treatment Phase and until 70 days after the last dose of study treatment

    • Acceptable methods include: copper intrauterine devices or double barrier methods, including male/female condoms with spermicide and use of contraceptive sponge, cervical cap, or diaphragm

16. Male patients must use an effective, non-hormonal form of contraception from screening throughout the treatment phase and until 130 days after last dose of study treatment

    • Acceptable methods include male/female condoms with spermicide, or vasectomy with medical confirmation of surgical success

17. Written informed consent and authorization to use and disclose health information
18. Ability to comprehend and comply with the requirements of the study

Exclusion Criteria:

1. Two or more prior chemotherapy regimens for advanced disease
2. Prior treatment with a taxane in the metastatic setting
3. Prior treatment with capecitabine at any dose
4. Current evidence of leptomeningeal disease
5. Other cancer that required therapy within the preceding 5 years other than adequately treated: (a) non-melanoma skin cancer or in situ cancer; or (b) following approval by the Medical Monitor, other cancer that has a very low risk of interfering with the safety or efficacy endpoints of the study
6. Known human immunodeficiency virus infection, unless well controlled. Patients who are on an adequate antiviral regimen with no evidence of active infection are considered well controlled.
7. Active hepatitis B or active hepatitis C infection
8. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study
9. Presence of neuropathy > Grade 1 per NCI CTCAE version 5.0
10. History of hypersensitivity to taxanes; hypersensitivity to the solvent does not preclude patient participation in this study
11. Anticancer treatment, including endocrine therapy, radiotherapy (except stereotactic brain radiosurgery), chemotherapy, biologic therapy, or therapy in an investigational clinical study, ≤ 14 days prior to the date of randomization
12. Major surgery ≤ 28 days prior to the date of randomization; patient must have complete recovery from surgery
13. Less than 2 weeks or 5 plasma half-lives (whichever is greater) since last use of a medication or ingestion of an agent, beverage or food that is a known clinically relevant strong inhibitor or known clinically relevant inducer of the cytochrome P450 (CYP) 3A pathway (patients should discontinue taking any regularly taken medication that is a strong inhibitor or inducer of the CYP3A pathway)
14. History of hypersensitivity or unexpected reactions to capecitabine, other fluoropyrimidine agents or any of their ingredients
15. Known dihydropyrimidine dehydrogenase (DPD) deficiency. Testing for DPD deficiency must be performed where required by local regulations, using a validated method that is approved by local health authorities.
16. Pregnant or breastfeeding
17. If, in the opinion of the Investigator, the patient is deemed unwilling or unable to comply with the requirements of the study
18. Treatment with brivudine, sorivudine or its chemically-related analogs ≤ 28 days prior to the date of randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Tesetaxel (oral) and capecitabine (oral); Tesetaxel (27 mg/m2) once every 21 days on Day 1 of each 21-day cycle; and capecitabine (825 mg/m2) twice daily (in the morning and evening after a meal, for a total daily dose of 1,650 mg/m2) beginning with the evening dose on Day 1 through the morning dose on Day 15 of each 21-day cycle	Drug: Tesetaxel and Capecitabine; Tesetaxel plus reduced dose of Capecitabine
Active Comparator: Arm B: Capecitabine (oral); Capecitabine (1,250 mg/m2) twice daily (in the morning and evening after a meal, for a total daily dose of 2,500 mg/m2) beginning with the evening dose on Day 1 through the morning dose on Day 15 of each 21-day cycle	Drug: Capecitabine; Capecitabine alone at approved dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PFS as assessed by the IRC	Approximately 2.5-3.0 years

Secondary Outcome Measures

Outcome Measure	Time Frame
OS	Approximately 5.0-5.5 years
ORR as assessed by the IRC	Approximately 2.5-3.0 years
DCR as assessed by the IRC	Approximately 2.5-3.0 years
Central nervous system (CNS) ORR as assessed by the CNS IRC in patients with CNS metastases at baseline	Approximately 2.5-3.0 years
CNS PFS as assessed by the CNS IRC in patients with CNS metastases at baseline or a history of CNS metastases and in the intent-to-treat (ITT) population	Approximately 2.5-3.0 years
CNS OS in patients with CNS metastases at baseline or a history of CNS metastases	Approximately 2.5-3.0 years

Other Outcome Measures

Outcome Measure	Time Frame
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Global Health Status/QoL	Approximately 2.5-3.0 years
EORTC QLQ-C30 Functional Scales and Symptom Scales/Items	Approximately 2.5-3.0 years
Adverse events, including deaths and other serious adverse events	Approximately 5.0-5.5 years
Incidence of clinical laboratory abnormalities (e.g., CBC, serum chemistry and coagulation testing)	Approximately 5.0-5.5 years
Peak plasma concentration (Cmax) of tesetaxel	Approximately 2.5-3.0 years
Area under the plasma concentration versus time curve (AUC) of tesetaxel	Approximately 2.5-3.0 years

Collaborators and Investigators

• Sponsor: Odonate Therapeutics, Inc.
• Investigators: Study Director: Joseph O'Connell, MD, Odonate Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2017
• Primary Completion (Actual): August 24, 2020
• Study Completion (Actual): June 28, 2021

Study Registration Dates

• First Submitted: October 13, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 26, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Capecitabine; Breast cancer; HER2 negative; Metastatic breast cancer; Tesetaxel; Taxanes; Hormone Receptor positive; Combination of tesetaxel and capecitabine; Locally advanced or metastatic breast cancer; Central nervous system (CNS) metastases
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: ODO-TE-B301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Currently under evaluation by the organization

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No