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

NCT01767155 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AEZS-108-050
• Study Type: interventional
• Target: 511
• Locations: 21 countries
• Sites: 119

Brief Summary

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

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Compare Efficacy Based on Objective Response Rate (ORR).

  3 years

• 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.

• Compare Efficacy Based on Clinical Benefit Rate (CBR).

  3 years

Study Arms (2)

AEZS-108 / zoptarelin doxorubicin

EXPERIMENTAL

267 mg/m\^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles up to 9 cycles

Drug: AEZS-108 / zoptarelin doxorubicin

doxorubicin/ standard chemotherapy

ACTIVE COMPARATOR

60 mg/m\^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles

Drug: doxorubicin

Interventions

AEZS-108 / zoptarelin doxorubicin DRUG

267 mg/m\^2 by 2-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles for a maximum of 9 cycles

Also known as: AEZS-108

AEZS-108 / zoptarelin doxorubicin

doxorubicin DRUG

60 mg/m\^2 by intravenous bolus injection or 1-hour intravenous infusion, on Day 1 of 21-day (3-week) cycles

doxorubicin/ standard chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AEterna Zentaris: lead

Study Sites (123)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

USC Norris Hospital and LAC+USC Medical Center

Los Angeles, California, 90033, United States

Location

University of California, Irvine - Medical Center

Orange, California, 92868-3200, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Women's Cancer Center

Covington, Louisiana, 70433, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medecine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Institute

New York, New York, 10065, United States

Location

Hope Women's Cancer Centers / Mission Hospital, Inc.

Asheville, North Carolina, 28806, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Peggy and Charles Oklahoma Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Hollings Cancer Center, MUSC

Charleston, South Carolina, 29425, United States

Location

Sanford Research/USD

Sioux Falls, South Dakota, 57104, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9179, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Inova Fairfax Hospitals

Falls Church, Virginia, 22024, United States

Location

Henrico Doctor's Hospital

Richmond, Virginia, 23229, United States

Location

Froedtert & The Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, 53226, United States

Location

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Alexandrov National Cancer centre of Belarus

Minsk, 223040, Belarus

Location

Minsk City Clinical Oncologic Dispensary

Minsk, Belarus

Location

Mogilev Regional Clinical Oncologic Dispensary

Mogilev, 212018, Belarus

Location

Vitebsk Regional Clinical Oncologic Dispensary

Vitebsk, 210603, Belarus

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

UZ Leuven - Campus Gasthuisberg

Leuven, Belgium

Location

Hospital Centre Liege University_CHU Sart Tilman

Liège, 4000, Belgium

Location

CHWAPI

Tournai, 7500, Belgium

Location

Clinical Center Banja Luka, Oncology Clinic

Banja Luka, 78000, Bosnia and Herzegovina

Location

University Clinical Hospital Mostar, Oncology clinic

Mostar, 88000, Bosnia and Herzegovina

Location

Clinical Centre University of Sarajevo

Sarajevo, 71000, Bosnia and Herzegovina

Location

Specialized Hospital for Active Treatment in Obstetrics and Gynecology

Pleven, Bulgaria

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Notre Dame - CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Hotel Dieu de Quebec- CHUQ

Québec, G1R 2J6, Canada

Location

Masarykův onkologický ústav

Brno, 65653, Czechia

Location

Fakultní nemocnice Olomouc

Olomouc, 77520, Czechia

Location

Všeobecná fakultní nemocnice v Praze

Prague, 12851, Czechia

Location

Copenhagen University Hospital "Rigshospitalet"

Copenhagen, 2100, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Kuopio University Hospital

Kuopio, 70029 KYS, Finland

Location

Tampere University Hospital

Tampere, 33521, Finland

Location

Turku University Central Hospital

Turku, 20521, Finland

Location

Universitätsklinikum Köln

Cologne, 50931, Germany

Location

Klinikum Frankfurt Höchst

Frankfurt, 65929, Germany

Location

Georg-August-Universität Göttingen, Universitäts-Frauenklinik, Abteilung für Gynäkologie und Geburtshilfe

Göttingen, Germany

Location

Universitätsklinik und Poliklinik für Gynäkologie Martin Luther Universität Halle-Wittenberg

Halle, 06097, Germany

Location

University Clinic Münster

Münster, 48149, Germany

Location

Klinik für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef

Regensburg, Germany

Location

Mater Misericordiae University Hospital

Dublin, 7, Ireland

Location

Mater Private Hospital

Dublin, 7, Ireland

Location

St James's Hospital

Dublin, 8, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Waterford Regional Hospital

Waterford, Ireland

Location

Barzilai Medical Center

Ashkelon, 78278, Israel

Location

Rambam Health Care Campus

Haifa, 31096, Israel

Location

Hadassah Hospital

Jerusalem, 91120, Israel

Location

Davidoff Center, Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Oncology Institute Kaplan

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 52661, Israel

Location

Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliero-Universitaria di Modena

Modena, 41124, Italy

Location

Istituto Nazionale Tumori IRCCS

Napoli, 80131, Italy

Location

Istituto Oncologico Veneto, IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, 61122, Italy

Location

Policlinico A. Gemelli

Rome, 00168, Italy

Location

Academic Medical Center

Amsterdam, 1105, Netherlands

Location

Maastricht University Medical Center (UMC)

Maastricht, 6229 HX, Netherlands

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

The Norwegian Radium Hospital

Oslo, 0310, Norway

Location

Helse Stavanger HF, Stavanger Universitetssjukhus

Stavanger, NO-4068, Norway

Location

Bialostockie Centrum Onkologii

Bialystok, 15-027, Poland

Location

Centrum Terapii Współczesnej ul.

Lodz, 90-242, Poland

Location

I Klinika Ginekologii Onkologicznej i Ginekologii

Lublin, 20-081, Poland

Location

Wojewodzki Szpital Specjalistyczny

Olsztyn, 10-561, Poland

Location

NZOZ Magodent, Szpital Onkologiczny

Warsaw, 03-291, Poland

Location

Oncolab

Craiova, Dolj, 200385, Romania

Location

Spitalul Clinic Judetean Mures

Târgu Mureş, Mureș County, 540072, Romania

Location

Oncology Institute "Prof. Dr. I. Chiricuta"

Cluj Npaoca, 400015, Romania

Location

Centru de Oncologie Sf. Nectarie

Craiova, Romania

Location

Spitalul Clinic Judetean de Urgenta "Sf. Ioan cel Nou"

Suceava, 720237, Romania

Location

Oncomed

Timișoara, 300239, Romania

Location

GAUZ "Republican Clinical Oncology Center"

Kazan', Tatarstan Republic, 420029, Russia

Location

FGBU "RONC n.a. N.N. Blokhin"

Moscow, 115478, Russia

Location

Nizhny Novgorod Regional Oncology Dispensary

Nizhny Novgorod, 603081, Russia

Location

Pyatigorsk Regional Oncology Dispensary

Pyatigorsk, Russia

Location

Budget Institution of Health / Leningrad Regional Oncological Dispensary

Saint Petersburg, 191014, Russia

Location

Saint-Petersburg State Budgetary Institution Healthcare "City Clinical Oncology Center"

Saint Petersburg, 198255, Russia

Location

FGBU "NIIO n.a. N.N. Petrov"

Saint Petersburg, Russia

Location

Republican Clinical Oncology Dispensary

Ufa, 450071, Russia

Location

Volgograd Regional Oncology Dispensary #3

Volzhskiy, Russia

Location

Hospital Vall d´Hebron

Barcelona, Spain

Location

MD Anderson cáncer center

Madrid, 28033, Spain

Location

Ramon Y Cajal Hospital

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28045, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Zina Memorial Cancer Hospital (LISSOD)

Plyuty, Kyiv Oblast, 08720, Ukraine

Location

Municipal institution "Dnipropetrovsk City Multidisciplinary Clinical Hospital No. 4"

Dnipro, 49102, Ukraine

Location

CCMP I Donetsk Regional Anticancer Center

Donetsk, 83092, Ukraine

Location

Public health enterprise "Kharkov regional Clinical Oncological Center"

Kharkiv, 61070, Ukraine

Location

Kiev City Clinical Oncology Center

Kiev, 03115, Ukraine

Location

Zakarpatskyi Regional Clinical Oncology Dispensary

Uzhhorod, 88014, Ukraine

Location

Vinnitsa Regional Clinical Oncology Dispensary

Vinnitsa, 21029, Ukraine

Location

The Royal Marsden Hospital NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JY, United Kingdom

Location

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, CV2 2DX, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Imperial college Healthcare NHS Trust

London, United Kingdom

Location

Nottingham City Hospital NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 36124638 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

LHRH, lysine(6)-doxorubicin; Doxorubicin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Dr. Nicola Ammer
• Organization: Aeterna Zentaris

nammer@aezsinc.com

+496942602

Study Officials

• David S Miller, MD

  University of Texas Southwestern Medical Center, Dallas, USA

  PRINCIPAL INVESTIGATOR

• Hani Gabra, MD

  Imperial College London Hammersmith Campus, London, UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 14, 2013
• Study Start: April 1, 2013
• Primary Completion: January 30, 2017
• Study Completion: January 30, 2017
• Last Updated: July 31, 2018
• Results First Posted: July 31, 2018

Record last verified: 2018-01

Locations

RU (9); AU (1); IT (6); BE (4); IE (5); DE (6); PL (5); BU (1); IL (7); NL (2); US (28); NO (3); CA (6); DK (2); FI (3); BO (3); CZ (3); ES (6); GB (6); RO (6); UA (7)