Clinical trial NCT01767155: Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer
Official title: Randomized Controlled Study Comparing AEZS-108 With Doxorubicin as Second Line Therapy for Locally Advanced, Recurrent or Metastatic Endometrial Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometrial Cancer
Lead sponsor: AEterna Zentaris
Sponsor class: INDUSTRY
First posted: 2013-01-14
Enrollment: 511
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: Open-label, randomized, active-controlled, two-arm Phase III study to compare the efficacy and safety of AEZS-108 and doxorubicin.

Detailed description: The study will include about 500 patients with endometrial cancer resistant to platinum/taxane-based chemotherapy.

Eligibility criteria: Inclusion Criteria:

1. Women ≥ 18 years of age
2. Histologically confirmed endometrial cancer
3. Advanced (FIGO stage III or IV), recurrent or metastatic disease.
4. Measurable or non-measurable disease that has progressed since last treatment.
5. 5. Patients with advanced, recurrent or metastatic endometrial cancer who have received one chemotherapeutic regimen with platinum and taxane (either as adjuvant or as first line treatment) and who have progressed.
6. Availability of fresh or archival FFPE (formalin-fixed and paraffin-embedded) tumor specimens for analysis of LHRH (luteinizing hormone releasing hormone) receptor expression.

Exclusion Criteria:

1. ECOG (Eastern Cooperative Oncology Group) performance status \> 2.
2. Inadequate hematologic, hepatic or renal function
3. Red blood cell transfusion within 2 weeks prior to anticipated start of study treatment.
4. History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
5. Impaired cardiac function defined as left ventricular ejection fraction (LVEF) \< 50 % (or below the study site's lower limit of normal) as measured by MUGA (multigated radionuclide angiography) or ECHO (echocardiography).
6. Concomitant use of prohibited therapy (specified in protocol)
7. Chemo-, immune-, or hormone-therapy within 5 elimination half life times or 4 weeks prior to randomization, whichever is the shorter. Radiotherapy (including pre- or post-operative brachytherapy) within 4 weeks prior to randomization.
8. Previous anthracycline-based chemotherapy (daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and valrubicin), in any formulation.
9. Anticipated ongoing concomitant anticancer therapy during the study.
10. History of serious co-morbidity or uncontrolled illness that would preclude study therapy, such as active tuberculosis or any other active infection.
11. Brain metastasis, leptomeningeal disease.
12. Pregnant or lactating female or female of child-bearing potential not employing adequate contraception.
13. Subjects with known hypersensitivity to peptide drugs, including LHRH agonists.
14. Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
15. Prior treatment with AEZS-108.
16. Use of LHRH agonist or antagonist treatment within 6 months prior to randomization.
17. Malignancy within last 5 years except non-melanoma skin cancer.
18. Any concomitant disease or condition which would interfere with the subjects' proper completion of the protocol assignment.
19. Concomitant or recent treatment with other investigational drug (within 4 weeks or 5 elimination half life times prior to anticipated start of study treatment).
20. Lack of ability or willingness to give informed consent.
21. Anticipated non-availability for study visits/procedures.

Primary outcomes:
measure: Compare the Overall Survival (OS) of Patients Treated With AEZS-108 to the OS of Patients Treated With Doxorubicin.
timeFrame: From randomization to death from any cause. During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks.
Secondary outcomes:
measure: Compare Efficacy Based on Objective Response Rate (ORR).
timeFrame: 3 years
measure: Compare Efficacy Based on Progression-free Survival (PFS).
timeFrame: During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks.
measure: Compare Efficacy Based on Clinical Benefit Rate (CBR).
timeFrame: 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: USC Norris Hospital and LAC+USC Medical Center
state: California
city: Orange
country: United States
facility: University of California, Irvine - Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Britain
country: United States
facility: The Hospital of Central Connecticut
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Covington
country: United States
facility: Women's Cancer Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medecine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Institute
state: New York
city: Asheville
country: United States
facility: Hope Women's Cancer Centers / Mission Hospital, Inc.
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Fargo
country: United States
facility: Roger Maris Cancer Center
state: North Dakota
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Peggy and Charles Oklahoma Cancer Center
state: Oklahoma
city: Charleston
country: United States
facility: Hollings Cancer Center, MUSC
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Research/USD
state: South Dakota
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospitals
state: Virginia
city: Richmond
country: United States
facility: Henrico Doctor's Hospital
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert & The Medical College of Wisconsin, Inc.
state: Wisconsin
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Minsk
country: Belarus
facility: Alexandrov National Cancer centre of Belarus
city: Minsk
country: Belarus
facility: Minsk City Clinical Oncologic Dispensary
city: Mogilev
country: Belarus
facility: Mogilev Regional Clinical Oncologic Dispensary
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncologic Dispensary
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven - Campus Gasthuisberg
city: Liege
country: Belgium
facility: Hospital Centre Liege University_CHU Sart Tilman
city: Tournai
country: Belgium
facility: CHWAPI
city: Banja Luka
country: Bosnia and Herzegovina
facility: Clinical Center Banja Luka, Oncology Clinic
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Hospital Mostar, Oncology clinic
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Centre University of Sarajevo
city: Pleven
country: Bulgaria
facility: Specialized Hospital for Active Treatment in Obstetrics and Gynecology
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre Dame - CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Quebec
country: Canada
facility: Hotel Dieu de Quebec- CHUQ
city: Brno
country: Czechia
facility: Masarykův onkologický ústav
city: Olomouc
country: Czechia
facility: Fakultní nemocnice Olomouc
city: Praha
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital "Rigshospitalet"
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Frankfurt
country: Germany
facility: Klinikum Frankfurt Höchst
city: Göttingen
country: Germany
facility: Georg-August-Universität Göttingen, Universitäts-Frauenklinik, Abteilung für Gynäkologie und Geburtshilfe
city: Halle
country: Germany
facility: Universitätsklinik und Poliklinik für Gynäkologie Martin Luther Universität Halle-Wittenberg
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Münster
country: Germany
facility: University Clinic Münster
city: Regensburg
country: Germany
facility: Klinik für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Hospital
city: Petah-Tikva
country: Israel
facility: Davidoff Center, Rabin Medical Center
city: Rehovot
country: Israel
facility: Oncology Institute Kaplan
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Bari
country: Italy
facility: Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS
city: Padova
country: Italy
facility: Istituto Oncologico Veneto, IRCCS
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord
city: Rome
country: Italy
facility: Policlinico A. Gemelli
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center (UMC)
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: The Norwegian Radium Hospital
city: Stavanger
country: Norway
facility: Helse Stavanger HF, Stavanger Universitetssjukhus
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologii
city: Lublin
country: Poland
facility: I Klinika Ginekologii Onkologicznej i Ginekologii
city: Olsztyn
country: Poland
facility: Wojewodzki Szpital Specjalistyczny
city: Warszawa
country: Poland
facility: NZOZ Magodent, Szpital Onkologiczny
city: Łódź
country: Poland
facility: Centrum Terapii Współczesnej ul.
city: Craiova
country: Romania
facility: Oncolab
state: Dolj County
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean Mures
state: Mures County
city: Cluj Npaoca
country: Romania
facility: Oncology Institute "Prof. Dr. I. Chiricuta"
city: Craiova
country: Romania
facility: Centru de Oncologie Sf. Nectarie
city: Suceava
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Ioan cel Nou"
city: Timisoara
country: Romania
facility: Oncomed
city: Kazan
country: Russian Federation
facility: GAUZ "Republican Clinical Oncology Center"
state: Republic Of Tatarstan
city: Moscow
country: Russian Federation
facility: FGBU "RONC n.a. N.N. Blokhin"
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Regional Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Regional Oncology Dispensary
city: Saint-Petersburg
country: Russian Federation
facility: FGBU "NIIO n.a. N.N. Petrov"
city: St. Petersburg
country: Russian Federation
facility: Budget Institution of Health / Leningrad Regional Oncological Dispensary
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg State Budgetary Institution Healthcare "City Clinical Oncology Center"
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary
city: Volzhskiy
country: Russian Federation
facility: Volgograd Regional Oncology Dispensary #3
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebron
city: Madrid
country: Spain
facility: MD Anderson cáncer center
city: Madrid
country: Spain
facility: Ramon Y Cajal Hospital
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Plyuty
country: Ukraine
facility: Zina Memorial Cancer Hospital (LISSOD)
state: Kiev Region
city: Dnepropetrovsk
country: Ukraine
facility: Municipal institution "Dnipropetrovsk City Multidisciplinary Clinical Hospital No. 4"
city: Donetsk
country: Ukraine
facility: CCMP I Donetsk Regional Anticancer Center
city: Kharkov
country: Ukraine
facility: Public health enterprise "Kharkov regional Clinical Oncological Center"
city: Kiev
country: Ukraine
facility: Kiev City Clinical Oncology Center
city: Uzhgorod
country: Ukraine
facility: Zakarpatskyi Regional Clinical Oncology Dispensary
city: Vinnitsa
country: Ukraine
facility: Vinnitsa Regional Clinical Oncology Dispensary
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital NHS Foundation Trust
state: Surrey
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
state: Wirral
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: London
country: United Kingdom
facility: Imperial college Healthcare NHS Trust
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
Study officials:
affiliation: University of Texas Southwestern Medical Center, Dallas, USA
name: David S Miller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London Hammersmith Campus, London, UK
name: Hani Gabra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mathews C, Lorusso D, Coleman RL, Boklage S, Garside J. An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer. Oncologist. 2022 Dec 9;27(12):1058-1066. doi: 10.1093/oncolo/oyac188.