Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer
- Conditions
- Endometrial Cancer
- Interventions
- Drug: AEZS-108 / zoptarelin doxorubicinDrug: doxorubicin
- Registration Number
- NCT01767155
- Lead Sponsor
- AEterna Zentaris
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 511
- Women ≥ 18 years of age
- Histologically confirmed endometrial cancer
- Advanced (FIGO stage III or IV), recurrent or metastatic disease.
- Measurable or non-measurable disease that has progressed since last treatment.
-
- 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.
- Availability of fresh or archival FFPE (formalin-fixed and paraffin-embedded) tumor specimens for analysis of LHRH (luteinizing hormone releasing hormone) receptor expression.
- ECOG (Eastern Cooperative Oncology Group) performance status > 2.
- Inadequate hematologic, hepatic or renal function
- Red blood cell transfusion within 2 weeks prior to anticipated start of study treatment.
- History of myocardial infarction, acute inflammatory heart disease, unstable angina, or uncontrolled arrhythmia within the past 6 months.
- 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).
- Concomitant use of prohibited therapy (specified in protocol)
- 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.
- Previous anthracycline-based chemotherapy (daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and valrubicin), in any formulation.
- Anticipated ongoing concomitant anticancer therapy during the study.
- History of serious co-morbidity or uncontrolled illness that would preclude study therapy, such as active tuberculosis or any other active infection.
- Brain metastasis, leptomeningeal disease.
- Pregnant or lactating female or female of child-bearing potential not employing adequate contraception.
- Subjects with known hypersensitivity to peptide drugs, including LHRH agonists.
- Receipt of 2 or more prior cytotoxic chemotherapy regimens for advanced, recurrent, or metastatic endometrial cancer.
- Prior treatment with AEZS-108.
- Use of LHRH agonist or antagonist treatment within 6 months prior to randomization.
- Malignancy within last 5 years except non-melanoma skin cancer.
- Any concomitant disease or condition which would interfere with the subjects' proper completion of the protocol assignment.
- Concomitant or recent treatment with other investigational drug (within 4 weeks or 5 elimination half life times prior to anticipated start of study treatment).
- Lack of ability or willingness to give informed consent.
- Anticipated non-availability for study visits/procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AEZS-108 / zoptarelin doxorubicin AEZS-108 / zoptarelin doxorubicin 267 mg/m\^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles up to 9 cycles doxorubicin/ standard chemotherapy doxorubicin 60 mg/m\^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles
- Primary Outcome Measures
Name Time Method Compare the Overall Survival (OS) of Patients Treated With AEZS-108 to the OS of Patients Treated With Doxorubicin. 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. Overall survival was defined as the elapsed time from randomization to death from any cause. For surviving patients, follow-up was to be censored at the date of last contact.
The final analysis, which was event-based, was conducted after approximately 384 randomized patients had died.
A log-rank test with an overall two sided Type I Error rate of 0.05 after taking the interim analyses into account was used to compare OS between the two treatment arms via a SAS (Statistical Analysis System) LIFETEST procedure. Kaplan Meier estimates were used to calculate median OS and the 95% confidence interval (CI) of the median OS. The proportion of patients alive at 6 and 12 months (from randomization date) and the 95% CIs for these estimated proportions were calculated.
- Secondary Outcome Measures
Name Time Method Compare Efficacy Based on Objective Response Rate (ORR). 3 years The ORR was defined as the sum of the Complete Response (CR) and Partial Response (PR).
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) was to have a reduction in the short axis to \<10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
All responses were confirmed at least 4 weeks after the initial response was observed. Tumor assessments occurred every 3 cycles (± 7 days) during ongoing treatment then every 3 months (± 7 days) thereafter while the patient was on study. The last assessment occurred either when progression was confirmed or when approximately 384 randomized patients had died.Compare Efficacy Based on Progression-free Survival (PFS). During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks. Progression-free survival (PFS): days between randomization and the date of documented progression or death for any cause that occurred up to the end of the study. For patients whose progression status could not be determined, their PFS data was censored for the last adequate progression assessment date that the patient was confirmed to have no progression.
Response and progression were to be evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Changes in the largest diameter (uni-dimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes were to be used.
During ongoing treatment, patients were to be re-evaluated for response every 3 cycles (i.e. every 9 weeks).
A subsequent scan was obtained no earlier than 4 weeks following the initial documentation of an objective status of either complete response (CR) or partial response (PR).Compare Efficacy Based on Clinical Benefit Rate (CBR). 3 years Clinical benefit was defined as having stable disease (SD) or better lasting for at least 9 weeks. The CBR was analyzed using the same methods for the ORR analyses. The analysis of CBR (CR+PR+SD) was performed in the ITT (intention-to-treat) population.
CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) was to have a reduction in the short axis to \<10 mm.
PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
All responses were confirmed at least 4 weeks after the initial response was observed. Tumor assessments occurred every 3 cycles (± 7 days) during ongoing treatment then every 3 months (± 7 days) thereafter while the patient was on study. The last assessment occurred either when progression was confirmed or when approximately 384 randomized patients had died.
Trial Locations
- Locations (123)
Hopital Notre Dame - CHUM
🇨🇦Montreal, Quebec, Canada
McGill University
🇨🇦Montreal, Quebec, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
Kuopio University Hospital
🇫🇮Kuopio, Finland
Centrum Terapii Współczesnej ul.
🇵🇱Łódź, Poland
Spitalul Clinic Judetean Mures
🇷🇴Targu Mures, Mures County, Romania
GAUZ "Republican Clinical Oncology Center"
🇷🇺Kazan, Republic Of Tatarstan, Russian Federation
Oncology Institute "Prof. Dr. I. Chiricuta"
🇷🇴Cluj Npaoca, Romania
FGBU "NIIO n.a. N.N. Petrov"
🇷🇺Saint-Petersburg, Russian Federation
Budget Institution of Health / Leningrad Regional Oncological Dispensary
🇷🇺St. Petersburg, Russian Federation
Saint-Petersburg State Budgetary Institution Healthcare "City Clinical Oncology Center"
🇷🇺St. Petersburg, Russian Federation
FGBU "RONC n.a. N.N. Blokhin"
🇷🇺Moscow, Russian Federation
Republican Clinical Oncology Dispensary
🇷🇺Ufa, Russian Federation
Nizhny Novgorod Regional Oncology Dispensary
🇷🇺Nizhny Novgorod, Russian Federation
Pyatigorsk Regional Oncology Dispensary
🇷🇺Pyatigorsk, Russian Federation
Volgograd Regional Oncology Dispensary #3
🇷🇺Volzhskiy, Russian Federation
Zina Memorial Cancer Hospital (LISSOD)
🇺🇦Plyuty, Kiev Region, Ukraine
CCMP I Donetsk Regional Anticancer Center
🇺🇦Donetsk, Ukraine
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Bebington, Wirral, United Kingdom
Kiev City Clinical Oncology Center
🇺🇦Kiev, Ukraine
Vinnitsa Regional Clinical Oncology Dispensary
🇺🇦Vinnitsa, Ukraine
Northwestern University
🇺🇸Chicago, Illinois, United States
Hope Women's Cancer Centers / Mission Hospital, Inc.
🇺🇸Asheville, North Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Institute
🇺🇸New York, New York, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
UZ Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Hospital Centre Liege University_CHU Sart Tilman
🇧🇪Liege, Belgium
Fakultní nemocnice Olomouc
🇨🇿Olomouc, Czechia
Turku University Central Hospital
🇫🇮Turku, Finland
Universitätsklinik und Poliklinik für Gynäkologie Martin Luther Universität Halle-Wittenberg
🇩🇪Halle, Germany
Hadassah Hospital
🇮🇱Jerusalem, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Davidoff Center, Rabin Medical Center
🇮🇱Petah-Tikva, Israel
Bialostockie Centrum Onkologii
🇵🇱Bialystok, Poland
The Norwegian Radium Hospital
🇳🇴Oslo, Norway
Haukeland University Hospital
🇳🇴Bergen, Norway
NZOZ Magodent, Szpital Onkologiczny
🇵🇱Warszawa, Poland
I Klinika Ginekologii Onkologicznej i Ginekologii
🇵🇱Lublin, Poland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Municipal institution "Dnipropetrovsk City Multidisciplinary Clinical Hospital No. 4"
🇺🇦Dnepropetrovsk, Ukraine
Public health enterprise "Kharkov regional Clinical Oncological Center"
🇺🇦Kharkov, Ukraine
The Royal Marsden Hospital NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Imperial college Healthcare NHS Trust
🇬🇧London, United Kingdom
Nottingham City Hospital NHS Trust
🇬🇧Nottingham, United Kingdom
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Peggy and Charles Oklahoma Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari
🇮🇹Bari, Italy
Istituto Nazionale Tumori IRCCS
🇮🇹Napoli, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
🇮🇹Pesaro, Italy
USC Norris Hospital and LAC+USC Medical Center
🇺🇸Los Angeles, California, United States
Women's Cancer Center
🇺🇸Covington, Louisiana, United States
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Mogilev Regional Clinical Oncologic Dispensary
🇧🇾Mogilev, Belarus
Mater Private Hospital
🇮🇪Dublin, Ireland
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Herlev Hospital
🇩🇰Herlev, Denmark
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Klinik für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef
🇩🇪Regensburg, Germany
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Washington University School of Medecine
🇺🇸Saint Louis, Missouri, United States
Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Alexandrov National Cancer centre of Belarus
🇧🇾Minsk, Belarus
CHWAPI
🇧🇪Tournai, Belgium
Clinical Center Banja Luka, Oncology Clinic
🇧🇦Banja Luka, Bosnia and Herzegovina
Hotel Dieu de Quebec- CHUQ
🇨🇦Quebec, Canada
Copenhagen University Hospital "Rigshospitalet"
🇩🇰Copenhagen, Denmark
Klinikum Frankfurt Höchst
🇩🇪Frankfurt, Germany
Georg-August-Universität Göttingen, Universitäts-Frauenklinik, Abteilung für Gynäkologie und Geburtshilfe
🇩🇪Göttingen, Germany
Institut Jules Bordet
🇧🇪Brussels, Belgium
University Clinical Hospital Mostar, Oncology clinic
🇧🇦Mostar, Bosnia and Herzegovina
Clinical Centre University of Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
Henrico Doctor's Hospital
🇺🇸Richmond, Virginia, United States
Sanford Research/USD
🇺🇸Sioux Falls, South Dakota, United States
Vitebsk Regional Clinical Oncologic Dispensary
🇧🇾Vitebsk, Belarus
Inova Fairfax Hospitals
🇺🇸Falls Church, Virginia, United States
Minsk City Clinical Oncologic Dispensary
🇧🇾Minsk, Belarus
Specialized Hospital for Active Treatment in Obstetrics and Gynecology
🇧🇬Pleven, Bulgaria
Princess Margaret Cancer Center
🇨🇦Toronto, Ontario, Canada
Masarykův onkologický ústav
🇨🇿Brno, Czechia
Všeobecná fakultní nemocnice v Praze
🇨🇿Praha, Czechia
Tampere University Hospital
🇫🇮Tampere, Finland
St James's Hospital
🇮🇪Dublin, Ireland
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Helse Stavanger HF, Stavanger Universitetssjukhus
🇳🇴Stavanger, Norway
Universitätsklinikum Köln
🇩🇪Köln, Germany
University Clinic Münster
🇩🇪Münster, Germany
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
University Hospital Galway
🇮🇪Galway, Ireland
Waterford Regional Hospital
🇮🇪Waterford, Ireland
Rambam Health Care Campus
🇮🇱Haifa, Israel
Chaim Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Spitalul Clinic Judetean de Urgenta "Sf. Ioan cel Nou"
🇷🇴Suceava, Romania
Oncomed
🇷🇴Timisoara, Romania
Istituto Oncologico Veneto, IRCCS
🇮🇹Padova, Italy
Policlinico A. Gemelli
🇮🇹Rome, Italy
Ramon Y Cajal Hospital
🇪🇸Madrid, Spain
Oncology Institute Kaplan
🇮🇱Rehovot, Israel
Maastricht University Medical Center (UMC)
🇳🇱Maastricht, Netherlands
Wojewodzki Szpital Specjalistyczny
🇵🇱Olsztyn, Poland
Azienda Ospedaliero-Universitaria di Modena
🇮🇹Modena, Italy
Hospital Vall d´Hebron
🇪🇸Barcelona, Spain
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Centru de Oncologie Sf. Nectarie
🇷🇴Craiova, Romania
Oncolab
🇷🇴Craiova, Dolj County, Romania
MD Anderson cáncer center
🇪🇸Madrid, Spain
Zakarpatskyi Regional Clinical Oncology Dispensary
🇺🇦Uzhgorod, Ukraine
University of California, Irvine - Medical Center
🇺🇸Orange, California, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Hollings Cancer Center, MUSC
🇺🇸Charleston, South Carolina, United States
Froedtert & The Medical College of Wisconsin, Inc.
🇺🇸Milwaukee, Wisconsin, United States
University Hospitals Coventry and Warwickshire NHS Trust
🇬🇧Coventry, United Kingdom
Medizinische Universität Innsbruck
🇦🇹Innsbruck, Austria