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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Placebo; Drug: Olaratumab; Drug: Doxorubicin

• Study Type: Interventional
• Enrollment (Actual): 509
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • BS
    • Caba, BS, Argentina, 1426
      • Alexander Fleming
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1125ABD
      • CENIT Centro de Neurociencias, Investigación y Tratamiento
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2002KDS
      • Hospital Provincial del Centenario
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
• Austria
  • Wien, Austria, 1090
    • AKH
• Belgium
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Brussel
    • Bruxelles, Brussel, Belgium, 1200
      • Cliniques Universitaires Saint-Luc
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20220-410
      • INCA Hospital do Câncer III
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01246-000
      • Icesp - Instituto Do Câncer Do Estado de São Paulo
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N2
      • Tom Baker Cancer Center
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Vancouver
  • Kowloon
    • Lai Chi Kok, Kowloon, Canada
      • Princess Margaret Hospital (Ontario)
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Royal Victoria Hospital-Montreal
• Denmark
  • Herlev, Denmark, 2730
    • Herlev and Gentofte Hospital
• Finland
  • Turku, Finland, SF-20520
    • Turku University Central Hospital
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33521
      • Tampereen yliopistollinen sairaala
• France
  • Bordeaux, France, 33076
    • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
  • Marseille CEDEX 05, France, 13385
    • CHU Hopital d'enfants de la Timone
  • Paris, France, 75248
    • Institut Curie
  • Toulouse cedex 9, France, 31059
    • Institut Claudius Regaud
  • Villejuif Cedex, France, 94805
    • Gustave Roussy
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • Centre Georges Francois Leclerc
  • Rhône-Alpes
    • Lyon, Rhône-Alpes, France, 69008
      • Centre Léon Bérard
• Germany
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68167
      • Klinikum Mannheim gGmbH Universitätsmedizin
    • Tubingen, Baden-Württemberg, Germany, 72076
      • Universitätsklinikum Tübingen
  • Bayern
    • Munchen, Bayern, Germany, 81377
      • Klinikum der Universität München Großhadern
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • Universitaetsklinikum Essen
• Hungary
  • Budapest, Hungary, 1062
    • Magyar Honvedseg Egeszsegugyi Kozpont
• Israel
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center
  • Tel Aviv Jaffa, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
  • Ramat Gan
    • Tel Hashomer, Ramat Gan, Israel, 5265601
      • Sheba Medical Center
• Italy
  • Lombardie
    • Milano, Lombardie, Italy, 20133
      • Istituto Nazionale dei Tumori
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • Università degli Studi di Catania - Azienda Policlinico
  • Torino
    • Candiolo, Torino, Italy, 10060
      • Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
• Japan
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital
  • Saitama
    • Hidaka, Saitama, Japan, 350-1298
      • Saitama Medical University International Medical Center
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan, 135-8550
      • Japanese Foundation for Cancer Research
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
  • Korea
    • Seoul, Korea, Korea, Republic of, 06591
      • Seoul St. Mary's Hospital
    • Seoul, Korea, Korea, Republic of, 05505
      • Asan Medical Center
• Mexico
  • San Luis Potosi, Mexico, 78213
    • Centro de Alta Especialidad Reumatologia Inv del Potosi SC
  • Baja California
    • Tijuana, Baja California, Mexico, 22010
      • Hospital Angeles
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil Fray Antonio Alcalde
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64320
      • Consultorio Dr. Reinoso
  • Yucatán
    • Merida, Yucatán, Mexico, 97134
      • Centro de Atención e Investigación Clínica en Oncología
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
  • Nijmegen, Netherlands, 6525 GA
    • Universitair Medisch Centrum St Radboud Nijmegen
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Medisch Centrum
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht UMC+
• Poland
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Blokhin Cancer Research Center
  • St. Petersburg, Russian Federation, 197758
    • St-Petersburg scientifical practical cente spec medical care
  • Tatarstan Republic
    • Kazan, Tatarstan Republic, Russian Federation, 420029
      • Kazan Oncology Dispensary
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08907
    • Hospital Duran I Reynals
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe de Valencia
  • Andalucía
    • Sevilla, Andalucía, Spain, 41013
      • Hospital Universitario Virgen Del Rocio
• Sweden
  • Lund, Sweden, 22185
    • Skånes universitetssjukhus Lund
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Sankt Gallen
    • St Gallen, Sankt Gallen, Switzerland, 9007
      • Cantonal Hospital St.Gallen
• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan Hsien, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, NW1 2BU
      • University College Hospital - London
    • London, Greater London, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Trust
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • The Christie NHS Foundation Trust
  • Merseyside
    • Bebbington, Merseyside, United Kingdom, CH63 4JY
      • The Clatterbridge Cancer Centre
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2SJ
      • Weston Park Hospital
• United States
  • California
    • Duarte, California, United States, 91010-0269
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90024
      • UCLA Medical Center
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center & Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30341
      • Georgia Cancer Specialists PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical School
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Cancer Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care Inc
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc
    • Cincinnati, Ohio, United States, 45202
      • Oncology Hematology Care Inc
    • Cincinnati, Ohio, United States, 45211
      • Oncology Hematology Care Inc
    • Fairfield, Ohio, United States, 45014
      • Oncology Hematology Care Inc
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology Hematology Associates
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
    • Nashville, Tennessee, United States, 37232-6307
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Oncology Hematology Care Inc
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
    • Salt Lake City, Utah, United States, 84112
      • University of Utah School of Medicine
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Fairfax Northern Virginia Hematology Oncology, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxorubicin + Olaratumab; 75 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.	Drug: Olaratumab; Administered IV; Other Names: LY3012207; Drug: Doxorubicin; Administered IV
Placebo Comparator: Doxorubicin + Placebo; 75 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.	Drug: Placebo; Administered IV; Drug: Doxorubicin; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS was defined by (Response Evaluation Criteria In Solid Tumors RECIST v.1.1) as the time from the date of randomization to the first date of radiologic disease progression or death due to any cause. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions. Censoring for death or PD due to increase sum of target lesions is defined for each participant as the time from the date of randomization to the first date of radiographic documentation of 1 or more lesions. Censoring for death without progression is defined as the date of death if there is no prior or concurrent radiologic disease progression.	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)	ORR was defined as the percentage of participants achieving a best overall response of complete response (CR) + partial response (PR). CR is the disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to RECIST v1.1.	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)	DCR was defined as the percentage of randomized participants achieving a best overall response of CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PD is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 45 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	Time to first worsening was calculated as the time from the first study drug dose to the first observation of worsening according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 total items covered by 1 of 3 dimensions (1 global health status/QoL total score, 5 functional subscales [physical, role, cognitive, emotional, and social]), and 9 symptom subscales [fatigue/nausea/vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea]). There are 28 questions answered on a 4-point scale where 1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). A linear transformation was used to obtain total score ranging from 0 to 100 where "worsening" was defined as an increase of at least 10 points for the symptom scales or a decrease of at least 10 points for the functional scales and the global health status/QoL scale.	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)	The EQ-5D-5L is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Health status was calculated from a set of item weights to derive a score of 0 to 1, with 1 representing the best health status. United Kingdom (UK) weights were applied. The analysis includes all cycles for which at least 25% of participants in each arm have an assessment. For each participant a change from baseline was calculated for every post-baseline assessment by subtracting the baseline assessment result from the current assessment result. Maximum improvement (over baseline) was determined from the set of all post-baseline change scores.	Randomization through Follow-up (Up to 35.8 Months)
Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"	Time to first worsening of the brief pain inventory short form modified (mBPI-sf) "worst pain score" was defined as the time from the date of the first study drug dose (baseline date) to the first date of a "worst pain" score increase of greater than or equal to (≥) 2 points from baseline. The mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes).	Randomization through Follow-up (Up to 34.5 Months)
Duration of Overall Response (DoR)	The duration of overall response was defined for each participant with a best response of CR or PR and measured from the time measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that disease is recurrent or objective disease progression or death due to any cause is observed (taking as reference for PD the smallest measurements recorded on study).	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 33.4 Months)
Duration of Disease Control (DDC)	Duration of disease control was defined for each participant with a best response of CR, PR, or stable disease (SD) as the time from randomization to the first date of disease progression or death due to any cause.	Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate	The PK systemic clearance parameter estimates from the current analysis are listed together with the population PK model estimates.	Cycle 1- 9: Day 1 and 8, Predose, 5 minutes Post dose and then every other cycle and follow-up (30 Days)
PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate	The PK parameter estimates from the current analysis are listed together with the population PK model estimates. The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2).	Cycle 1- 9: Day 1 and 8; Predose, 5 Minutes Post dose and then every other cycle and follow-up (30 Days)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: 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

Publications and helpful links

General Publications

• 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.
• Tap 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.
• Tobias 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.

Helpful Links

• A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2015
• Primary Completion (Actual): December 5, 2018
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 20, 2015
• First Posted (Estimated): May 22, 2015

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: leiomyosarcoma; doxorubicin; liposarcoma; soft tissue sarcoma (STS); metastatic soft tissue sarcoma; advanced soft tissue sarcoma; undifferentiated pleomorphic sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Olaratumab
• Other Study ID Numbers: 15677; I5B-MC-JGDJ (Other Identifier: Eli Lilly and Company); 2015-000134-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR