Zoptarelin Doxorubicin (AEZS 108) as Second Line Therapy for Endometrial Cancer

Endometrial Cancer Clinical Trial

— ZoptEC  

Official title:

Randomized Controlled Study Comparing AEZS-108 With Doxorubicin as Second Line Therapy for Locally Advanced, Recurrent or Metastatic Endometrial Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01767155
• Other study ID #: AEZS-108-050
• Status: Completed
• Phase: Phase 3
• Start date: April 2013
• Est. completion date: January 30, 2017

Study information

• Verified date: January 2018
• Source: AEterna Zentaris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open-label, randomized, active-controlled, two-arm Phase III study to compare the efficacy and safety of AEZS-108 and doxorubicin.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 511
• Est. completion date: January 30, 2017
• Est. primary completion date: January 30, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• AEZS-108 / zoptarelin doxorubicin
267 mg/m^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles for a maximum of 9 cycles
• doxorubicin
60 mg/m^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Belarus	Alexandrov National Cancer centre of Belarus	Minsk
Belarus	Minsk City Clinical Oncologic Dispensary	Minsk
Belarus	Mogilev Regional Clinical Oncologic Dispensary	Mogilev
Belarus	Vitebsk Regional Clinical Oncologic Dispensary	Vitebsk
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Leuven - Campus Gasthuisberg	Leuven
Belgium	Hospital Centre Liege University_CHU Sart Tilman	Liege
Belgium	CHWAPI	Tournai
Bosnia and Herzegovina	Clinical Center Banja Luka, Oncology Clinic	Banja Luka
Bosnia and Herzegovina	University Clinical Hospital Mostar, Oncology clinic	Mostar
Bosnia and Herzegovina	Clinical Centre University of Sarajevo	Sarajevo
Bulgaria	Specialized Hospital for Active Treatment in Obstetrics and Gynecology	Pleven
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hopital Notre Dame - CHUM	Montreal	Quebec
Canada	McGill University	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Hotel Dieu de Quebec- CHUQ	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Czechia	Masarykuv onkologický ústav	Brno
Czechia	Fakultní nemocnice Olomouc	Olomouc
Czechia	Všeobecná fakultní nemocnice v Praze	Praha
Denmark	Copenhagen University Hospital "Rigshospitalet"	Copenhagen
Denmark	Herlev Hospital	Herlev
Finland	Kuopio University Hospital	Kuopio
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku
Germany	Klinikum Frankfurt Höchst	Frankfurt
Germany	Georg-August-Universität Göttingen, Universitäts-Frauenklinik, Abteilung für Gynäkologie und Geburtshilfe	Göttingen
Germany	Universitätsklinik und Poliklinik für Gynäkologie Martin Luther Universität Halle-Wittenberg	Halle
Germany	Universitätsklinikum Köln	Köln
Germany	University Clinic Münster	Münster
Germany	Klinik für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef	Regensburg
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	Mater Private Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	Waterford Regional Hospital	Waterford
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Hospital	Jerusalem
Israel	Davidoff Center, Rabin Medical Center	Petah-Tikva
Israel	Oncology Institute Kaplan	Rehovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Chaim Sheba Medical Center	Tel Hashomer
Italy	Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari	Bari
Italy	Azienda Ospedaliero-Universitaria di Modena	Modena
Italy	Istituto Nazionale Tumori IRCCS	Napoli
Italy	Istituto Oncologico Veneto, IRCCS	Padova
Italy	Azienda Ospedaliera Ospedali Riuniti Marche Nord	Pesaro
Italy	Policlinico A. Gemelli	Rome
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Maastricht University Medical Center (UMC)	Maastricht
Norway	Haukeland University Hospital	Bergen
Norway	The Norwegian Radium Hospital	Oslo
Norway	Helse Stavanger HF, Stavanger Universitetssjukhus	Stavanger
Poland	Bialostockie Centrum Onkologii	Bialystok
Poland	Centrum Terapii Wspólczesnej ul.	Lódz
Poland	I Klinika Ginekologii Onkologicznej i Ginekologii	Lublin
Poland	Wojewodzki Szpital Specjalistyczny	Olsztyn
Poland	NZOZ Magodent, Szpital Onkologiczny	Warszawa
Romania	Oncology Institute "Prof. Dr. I. Chiricuta"	Cluj Npaoca
Romania	Centru de Oncologie Sf. Nectarie	Craiova
Romania	Oncolab	Craiova	Dolj County
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Ioan cel Nou"	Suceava
Romania	Spitalul Clinic Judetean Mures	Targu Mures	Mures County
Romania	Oncomed	Timisoara
Russian Federation	GAUZ "Republican Clinical Oncology Center"	Kazan	Republic Of Tatarstan
Russian Federation	FGBU "RONC n.a. N.N. Blokhin"	Moscow
Russian Federation	Nizhny Novgorod Regional Oncology Dispensary	Nizhny Novgorod
Russian Federation	Pyatigorsk Regional Oncology Dispensary	Pyatigorsk
Russian Federation	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	Republican Clinical Oncology Dispensary	Ufa
Russian Federation	Volgograd Regional Oncology Dispensary #3	Volzhskiy
Spain	Hospital Vall d´Hebron	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	MD Anderson cáncer center	Madrid
Spain	Ramon Y Cajal Hospital	Madrid
Spain	Instituto Valenciano de Oncologia	Valencia
Ukraine	Municipal institution "Dnipropetrovsk City Multidisciplinary Clinical Hospital No. 4"	Dnepropetrovsk
Ukraine	CCMP I Donetsk Regional Anticancer Center	Donetsk
Ukraine	Public health enterprise "Kharkov regional Clinical Oncological Center"	Kharkov
Ukraine	Kiev City Clinical Oncology Center	Kiev
Ukraine	Zina Memorial Cancer Hospital (LISSOD)	Plyuty	Kiev Region
Ukraine	Zakarpatskyi Regional Clinical Oncology Dispensary	Uzhgorod
Ukraine	Vinnitsa Regional Clinical Oncology Dispensary	Vinnitsa
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Bebington	Wirral
United Kingdom	University Hospitals Coventry and Warwickshire NHS Trust	Coventry
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	The Royal Marsden Hospital NHS Foundation Trust	Sutton	Surrey
United States	Hope Women's Cancer Centers / Mission Hospital, Inc.	Asheville	North Carolina
United States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Hollings Cancer Center, MUSC	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Women's Cancer Center	Covington	Louisiana
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Inova Fairfax Hospitals	Falls Church	Virginia
United States	Roger Maris Cancer Center	Fargo	North Dakota
United States	Hartford Hospital	Hartford	Connecticut
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	USC Norris Hospital and LAC+USC Medical Center	Los Angeles	California
United States	Froedtert & The Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Memorial Sloan-Kettering Cancer Institute	New York	New York
United States	Peggy and Charles Oklahoma Cancer Center	Oklahoma City	Oklahoma
United States	University of California, Irvine - Medical Center	Orange	California
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Henrico Doctor's Hospital	Richmond	Virginia
United States	Washington University School of Medecine	Saint Louis	Missouri
United States	Sanford Research/USD	Sioux Falls	South Dakota
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AEterna Zentaris

Countries where clinical trial is conducted

United States,  Austria,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Canada,  Czechia,  Denmark,  Finland,  Germany,  Ireland,  Israel,  Italy,  Netherlands,  Norway,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the Overall Survival (OS) of Patients Treated With AEZS-108 to the OS of Patients Treated With Doxorubicin.	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.	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	Compare Efficacy Based on Objective Response Rate (ORR).	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.	3 years
Secondary	Compare Efficacy Based on Progression-free Survival (PFS).	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).	During ongoing treatment: response evaluation every 3 cycles. For patients gone of treatment: re-assessment every 12 weeks.
Secondary	Compare Efficacy Based on Clinical Benefit Rate (CBR).	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.	3 years