A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma
ANNOUNCE
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Doxorubicin Plus Olaratumab Versus Doxorubicin Plus Placebo in Patients With Advanced or Metastatic Soft Tissue Sarcoma
3 other identifiers
interventional
509
24 countries
113
Brief Summary
The main purpose of this study is to evaluate the efficacy of the combination of doxorubicin plus the study drug known as olaratumab versus doxorubicin plus placebo in participants with advanced or metastatic soft tissue sarcoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2015
Longer than P75 for phase_3
113 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2015
CompletedFirst Posted
Study publicly available on registry
May 22, 2015
CompletedStudy Start
First participant enrolled
September 14, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 5, 2018
CompletedResults Posted
Study results publicly available
December 17, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 27, 2024
CompletedJuly 15, 2025
June 1, 2025
3.2 years
May 20, 2015
November 27, 2019
June 27, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall Survival (OS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. For each participant, prior to data analysis, a reasonable effort was made to obtain the most up-to-date status (date of death or last date known to be alive). For any participant not known to have died as of the data cutoff date, OS was censored at the date the participant was last known to be alive. For any participant who withdrew consent for survival follow-up, OS was censored at the last date for which the participant provided consent for follow-up contact. The Kaplan-Meier method was used to estimate median parameters.
Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Overall Survival (OS) Leiomyosarcoma (LMS)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. For each participant, prior to data analysis, a reasonable effort was made to obtain the most up-to-date status (date of death or last date known to be alive). For any participant not known to have died as of the data cutoff date, OS was censored at the date the participant was last known to be alive. For any participant who withdrew consent for survival follow-up, OS was censored at the last date for which the participant provided consent for follow-up contact. The Kaplan-Meier method was used to estimate median parameters.
Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Secondary Outcomes (10)
Progression Free Survival (PFS)
Randomization to Objective Progression or Death Due to Any Cause (Up to 35.8 Months)
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.5 Months)
Time to First Worsening on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores
Randomization (Cycle 1) through Follow-up (Up to 35.8 Months)
Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)
Randomization through Follow-up (Up to 35.8 Months)
- +5 more secondary outcomes
Study Arms (2)
Doxorubicin + Olaratumab
EXPERIMENTAL75 milligrams per meter squared (mg/m\^2) doxorubicin administered intravenously (IV) on day 1 of each 21-day cycle for 8 cycles plus 20 milligrams per kilogram (mg/kg) dose of olaratumab administered IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab administered IV on day 1 and day 8 of cycles 2-8. Beginning with cycle 9, 15 mg/kg olaratumab administered IV on day 1 and day 8 of each subsequent 21-day cycle until documented progressive disease (PD) or discontinuation for any other reason.
Doxorubicin + Placebo
PLACEBO COMPARATOR75 mg/m\^2 doxorubicin administered IV on day 1 of each 21-day cycle for 8 cycles plus placebo (equivalent volume) administered IV on day 1 and day 8 for 8 cycles. Beginning with cycle 9, placebo (equivalent volume) administered on days 1 and 8 of each subsequent 21-day cycle until PD or discontinuation for any other reason.
Interventions
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of advanced unresectable or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Note: Evidence of disease progression is required for participants that are not newly diagnosed.
- Presence of measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1, Eisenhauer et al. 2009).
- Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
- The participant has not received any previous treatment with anthracyclines.
- The participant may have had any number of prior systemic cytotoxic therapies for advanced/metastatic disease and are considered appropriate candidates for anthracycline therapy. All previous anticancer treatments must be completed ≥ 3 weeks (21 days) prior to first dose of study drug.
- Availability of tumor tissue is required for study eligibility. The participant must have consented to provide archived formalin-fixed paraffin embedded (FFPE) tumor tissue or be subject to a pre-treatment re-biopsy of primary or metastatic tumor tissue for future central pathology review and translational research (if archived tissue is unavailable).
- Adequate hematologic, organ, and coagulation within 2 weeks (14 days) prior to randomization.
- Left ventricular ejection fraction (LVEF) ≥50% assessed within 28 days prior to randomization.
- Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
- Females of child-bearing potential and males must agree to use highly effective contraceptive precautions during the trial and up to 3 months following the last dose of study drug.
- The participant has, in the opinion of the investigator, a life expectancy of at least 3 months.
You may not qualify if:
- Diagnosis of GIST or Kaposi sarcoma.
- Active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of randomization. Participants with a history of a CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days and are not receiving systemic corticosteroids and or/anticonvulsants, are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before randomization to rule out brain metastasis.
- Prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones; the participant has received treatment with olaratumab or has participated in a prior olaratumab trial.
- Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.
- The participant has symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF \< 50%), severe myocardial insufficiency, cardiac arrhythmia, or cardiomyopathy.
- The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months of randomization.
- The participant has a QT interval calculated using Bazett's formula (QTcB) interval of \>450 milliseconds (msec) for males and \>470 msec for females on screening electrocardiogram (ECG).
- Females who are pregnant or breastfeeding.
- Known allergy to any of the treatment components including a history of allergic reactions attributed to compounds of chemical or biological composition similar to olaratumab.
- The participant has a known active fungal, bacterial, or viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (114)
City of Hope National Medical Center
Duarte, California, 91010-0269, United States
UCLA Medical Center
Los Angeles, California, 90024, United States
Stanford University
Stanford, California, 94305, United States
University of Colorado Cancer Center
Aurora, Colorado, 80045, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224, United States
Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
Georgia Cancer Specialists PC
Atlanta, Georgia, 30341, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Washington University Medical School
St Louis, Missouri, 63110, United States
Nebraska Methodist Cancer Center
Omaha, Nebraska, 68114, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87102, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke Cancer Institute
Durham, North Carolina, 27710, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45202, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45211, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45230, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, 45236, United States
Oncology Hematology Care Inc
Fairfield, Ohio, 45014, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, 19106, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
The West Clinic
Germantown, Tennessee, 38138, United States
Oncology Hematology Care Inc
Nashville, Tennessee, 37203, United States
Tennessee Oncology PLLC
Nashville, Tennessee, 37203, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-6307, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
University of Utah School of Medicine
Salt Lake City, Utah, 84112, United States
Fairfax Northern Virginia Hematology Oncology, PC
Fairfax, Virginia, 22031, United States
Alexander Fleming
CABA, BS, 1426, Argentina
CENIT Centro de Neurociencias, Investigación y Tratamiento
Caba, Buenos Aires, C1125ABD, Argentina
Hospital Provincial del Centenario
Rosario, Santa Fe Province, S2002KDS, Argentina
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
AKH
Vienna, 1090, Austria
Cliniques universitaires Saint-Luc
Brussels, Brussels Capital, 1200, Belgium
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, 9000, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, 3000, Belgium
INCA Hospital do Câncer III
Rio de Janeiro, Rio de Janeiro, 20220-410, Brazil
Icesp - Instituto Do Câncer Do Estado de São Paulo
São Paulo, São Paulo, 01246-000, Brazil
Tom Baker Cancer Center
Calgary, Alberta, T2N4N2, Canada
BC Cancer Vancouver
Vancouver, British Columbia, V5Z 4E6, Canada
Princess Margaret Hospital (Ontario)
Lai Chi Kok, Kowloon, Canada
Royal Victoria Hospital-Montreal
Montreal, Quebec, H4A 3J1, Canada
Herlev and Gentofte Hospital
Herlev, 2730, Denmark
Tampereen yliopistollinen sairaala
Tampere, Pirkanmaa, 33521, Finland
Turku University Central Hospital
Turku, SF-20520, Finland
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69008, France
Centre Georges François Leclerc
Dijon, Côte-d'Or, 21079, France
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux, 33076, France
CHU Hopital d'enfants de la Timone
Marseille, 13385, France
Institut Curie
Paris, 75248, France
Institut Claudius Regaud
Toulouse, 31059, France
Gustave Roussy
Villejuif, 94805, France
Klinikum Mannheim gGmbH Universitätsmedizin
Mannheim, Baden-Wurttemberg, 68167, Germany
Universitätsklinikum Tübingen
Tübingen, Baden-Wurttemberg, 72076, Germany
Klinikum der Universität München Großhadern
München, Bavaria, 81377, Germany
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45122, Germany
HELIOS Klinikum Berlin-Buch
Berlin, 13125, Germany
Magyar Honvedseg Egeszsegugyi Kozpont
Budapest, 1062, Hungary
Sheba Medical Center
Tel Litwinsky, Ramat Gan, 5265601, Israel
Hadassah Medical Center
Jerusalem, 9112001, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Istituto Nazionale dei Tumori
Milan, Lombardy, 20133, Italy
Istituto Clinico Humanitas
Rozzano, Milano, 20089, Italy
Università degli Studi di Catania - Azienda Policlinico
Catania, Sicily, 95123, Italy
Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
Candiolo, Torino, 10060, Italy
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804, Japan
Osaka University Hospital
Suita, Osaka, 565-0871, Japan
Saitama Medical University International Medical Center
Hidaka, Saitama, 350-1298, Japan
National Cancer Center Hospital
Chuo-Ku, Tokyo, 104-0045, Japan
Japanese Foundation for Cancer Research
Koto-ku, Tokyo, 135-8550, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, 811-1395, Japan
Okayama University Hospital
Okayama, 700-8558, Japan
National Hospital Organization Osaka National Hospital
Osaka, 540-0006, Japan
Osaka International Cancer Institute
Osaka, 541-8567, Japan
Hospital Angeles
Tijuana, Estado de Baja California, 22010, Mexico
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, 44280, Mexico
Consultorio Dr. Reinoso
Monterrey, Nuevo León, 64320, Mexico
Centro de Atención E Investigación Clínica En Oncología
Mérida, Yucatán, 97134, Mexico
Centro de Alta Especialidad Reumatologia Inv del Potosi SC
San Luis Potosí City, 78213, Mexico
Maastricht UMC+
Maastricht, Limburg, 6229 HX, Netherlands
University Medical Center Groningen
Groningen, 9713 GZ, Netherlands
Leids Universitair Medisch Centrum
Leiden, 2333 ZA, Netherlands
Universitair Medisch Centrum St Radboud Nijmegen
Nijmegen, 6525 GA, Netherlands
Erasmus Medisch Centrum
Rotterdam, 3015 GD, Netherlands
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Warsaw, 02-781, Poland
Kazan Oncology Dispensary
Kazan', Tatarstan Republic, 420029, Russia
Blokhin Cancer Research Center
Moscow, 115478, Russia
St-Petersburg scientifical practical cente spec medical care
Saint Petersburg, 197758, Russia
National Cancer Center
Goyang-si, Gyeonggi-do, 10408, South Korea
Asan Medical Center
Seoul, Korea, 05505, South Korea
Seoul St. Mary's Hospital
Seoul, Korea, 06591, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital Universitario Virgen Del Rocio
Seville, Andalusia, 41013, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Duran I Reynals
Barcelona, 08907, Spain
Hospital Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Universitario La Fe de Valencia
Valencia, 46026, Spain
Skånes universitetssjukhus Lund
Lund, 22185, Sweden
Cantonal Hospital St.Gallen
Sankt Gallen, Canton of St. Gallen, 9007, Switzerland
Inselspital Bern
Bern, 3010, Switzerland
National Taiwan University Hospital
Taipei, 10002, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Chang Gung Memorial Hospital - Linkou
Taoyuan Hsien, 333, Taiwan
University College Hospital - London
London, Greater London, NW1 2BU, United Kingdom
Royal Marsden NHS Trust
London, Greater London, SW3 6JJ, United Kingdom
The Christie NHS Foundation Trust
Manchester, Greater Manchester, M20 4BX, United Kingdom
The Clatterbridge Cancer Centre
Bebbington, Merseyside, CH63 4JY, United Kingdom
Weston Park Hospital
Sheffield, South Yorkshire, S10 2SJ, United Kingdom
Related Publications (3)
Jones RL, Wagner AJ, Kawai A, Tamura K, Shahir A, Van Tine BA, Martin-Broto J, Peterson PM, Wright J, Tap WD. Prospective Evaluation of Doxorubicin Cardiotoxicity in Patients with Advanced Soft-tissue Sarcoma Treated in the ANNOUNCE Phase III Randomized Trial. Clin Cancer Res. 2021 Jul 15;27(14):3861-3866. doi: 10.1158/1078-0432.CCR-20-4592. Epub 2021 Feb 25.
PMID: 33632930DERIVEDTap WD, Wagner AJ, Schoffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, Yen CC, Abdul Razak AR, Spira A, Kawai A, Le Cesne A, Van Tine BA, Naito Y, Park SH, Fedenko A, Papai Z, Soldatenkova V, Shahir A, Mo G, Wright J, Jones RL; ANNOUNCE Investigators. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1266-1276. doi: 10.1001/jama.2020.1707.
PMID: 32259228DERIVEDTobias A, O'brien MP, Agulnik M. Olaratumab for advanced soft tissue sarcoma. Expert Rev Clin Pharmacol. 2017 Jul;10(7):699-705. doi: 10.1080/17512433.2017.1324295. Epub 2017 May 5.
PMID: 28447475DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 20, 2015
First Posted
May 22, 2015
Study Start
September 14, 2015
Primary Completion
December 5, 2018
Study Completion
June 27, 2024
Last Updated
July 15, 2025
Results First Posted
December 17, 2019
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.