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

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified May 2025 by Eli Lilly and Company
Sponsor
Eli Lilly and Company
Information Provided by (Responsible Party)
Eli Lilly and Company
Clinicaltrials.gov Identifier
NCT02451943
Other Study ID Numbers:
15677
First Submitted
May 19, 2015
First Posted
May 21, 2015
Results First Posted
November 26, 2019
Last Update Posted
July 14, 2025
Last Verified
May 2025

ClinicalTrials.gov processed this data on June 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Soft Tissue Sarcoma
Drug: OlaratumabDrug: Doxorubicin

Study Design

Study TypeInterventional
Actual Enrollment509 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA 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
Study Start DateSeptember 13, 2015
Actual Primary Completion DateDecember 4, 2018
Actual Study Completion DateJune 26, 2024

Groups and Cohorts

Group/CohortIntervention/Treatment
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
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: Doxorubicin
Administered IV

Outcome Measures

Primary Outcome Measures
  1. 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.
  2. 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.
Secondary Outcome Measures
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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).
  7. 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).
  8. 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.
  9. 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.
  10. 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).

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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).

Contacts and Locations

Sponsors and CollaboratorsEli Lilly and Company
Locations
City of Hope National Medical Center | Duarte California, United States, 91010-0269UCLA Medical Center | Los Angeles California, United States, 90024Stanford University | Stanford California, United States, 94305University of Colorado Cancer Center | Aurora Colorado, United States, 80045Mayo Clinic in Florida | Jacksonville Florida, United States, 32224Moffitt Cancer Center & Research Institute | Tampa Florida, United States, 33612Georgia Cancer Specialists PC | Atlanta Georgia, United States, 30341Dana Farber Cancer Institute | Boston Massachusetts, United States, 02215University of Michigan | Ann Arbor Michigan, United States, 48109Washington University Medical School | St Louis Missouri, United States, 63110Nebraska Methodist Cancer Center | Omaha Nebraska, United States, 68114University of New Mexico Cancer Center | Albuquerque New Mexico, United States, 87102Columbia University Medical Center | New York New York, United States, 10032Memorial Sloan Kettering Cancer Center | New York New York, United States, 10065Duke Cancer Institute | Durham North Carolina, United States, 27710Oncology Hematology Care Inc | Cincinnati Ohio, United States, 45202Oncology Hematology Care Inc | Cincinnati Ohio, United States, 45211Oncology Hematology Care Inc | Cincinnati Ohio, United States, 45230Oncology Hematology Care Inc | Cincinnati Ohio, United States, 45236Oncology Hematology Care Inc | Fairfield Ohio, United States, 45014Oregon Health and Science University | Portland Oregon, United States, 97239Pennsylvania Oncology Hematology Associates | Philadelphia Pennsylvania, United States, 19106University of Pittsburgh Medical Center | Pittsburgh Pennsylvania, United States, 15232The West Clinic | Germantown Tennessee, United States, 38138Oncology Hematology Care Inc | Nashville Tennessee, United States, 37203Tennessee Oncology PLLC | Nashville Tennessee, United States, 37203Vanderbilt University Medical Center | Nashville Tennessee, United States, 37232-6307Utah Cancer Specialists | Salt Lake City Utah, United States, 84106University of Utah School of Medicine | Salt Lake City Utah, United States, 84112Fairfax Northern Virginia Hematology Oncology, PC | Fairfax Virginia, United States, 22031Alexander Fleming | CABA BS, Argentina, 1426CENIT Centro de Neurociencias, Investigación y Tratamiento | Caba Buenos Aires, Argentina, C1125ABDHospital Provincial del Centenario | Rosario Santa Fe Province, Argentina, S2002KDSChris O'Brien Lifehouse | Camperdown New South Wales, Australia, 2050AKH | Vienna , Austria, 1090Cliniques universitaires Saint-Luc | Brussels Brussels Capital, Belgium, 1200Universitair Ziekenhuis Gent | Ghent Oost-Vlaanderen, Belgium, 9000Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven , Belgium, 3000INCA Hospital do Câncer III | Rio de Janeiro Rio de Janeiro, Brazil, 20220-410Icesp - Instituto Do Câncer Do Estado de São Paulo | São Paulo São Paulo, Brazil, 01246-000Tom Baker Cancer Center | Calgary Alberta, Canada, T2N4N2BC Cancer Vancouver | Vancouver British Columbia, Canada, V5Z 4E6Princess Margaret Hospital (Ontario) | Lai Chi Kok Kowloon, Canada, Royal Victoria Hospital-Montreal | Montreal Quebec, Canada, H4A 3J1Herlev and Gentofte Hospital | Herlev , Denmark, 2730Tampereen yliopistollinen sairaala | Tampere Pirkanmaa, Finland, 33521Turku University Central Hospital | Turku , Finland, SF-20520Centre Leon Berard | Lyon Auvergne-Rhône-Alpes, France, 69008Centre Georges François Leclerc | Dijon Côte-d'Or, France, 21079Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest | Bordeaux , France, 33076CHU Hopital d'enfants de la Timone | Marseille , France, 13385Institut Curie | Paris , France, 75248Institut Claudius Regaud | Toulouse , France, 31059Gustave Roussy | Villejuif , France, 94805Klinikum Mannheim gGmbH Universitätsmedizin | Mannheim Baden-Wurttemberg, Germany, 68167Universitätsklinikum Tübingen | Tübingen Baden-Wurttemberg, Germany, 72076Klinikum der Universität München Großhadern | München Bavaria, Germany, 81377Universitaetsklinikum Essen | Essen North Rhine-Westphalia, Germany, 45122HELIOS Klinikum Berlin-Buch | Berlin , Germany, 13125Magyar Honvedseg Egeszsegugyi Kozpont | Budapest , Hungary, 1062Sheba Medical Center | Tel Litwinsky Ramat Gan, Israel, 5265601Hadassah Medical Center | Jerusalem , Israel, 9112001Tel Aviv Sourasky Medical Center | Tel Aviv , Israel, 6423906Istituto Nazionale dei Tumori | Milan Lombardy, Italy, 20133Istituto Clinico Humanitas | Rozzano Milano, Italy, 20089Università degli Studi di Catania - Azienda Policlinico | Catania Sicily, Italy, 95123Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia | Candiolo Torino, Italy, 10060Nagoya University Hospital | Nagoya Aichi-ken, Japan, 466-8560National Cancer Center Hospital East | Kashiwa Chiba, Japan, 277-8577National Hospital Organization Hokkaido Cancer Center | Sapporo Hokkaido, Japan, 003-0804Osaka University Hospital | Suita Osaka, Japan, 565-0871Saitama Medical University International Medical Center | Hidaka Saitama, Japan, 350-1298National Cancer Center Hospital | Chuo-Ku Tokyo, Japan, 104-0045Japanese Foundation for Cancer Research | Koto-ku Tokyo, Japan, 135-8550National Hospital Organization Kyushu Cancer Center | Fukuoka , Japan, 811-1395Okayama University Hospital | Okayama , Japan, 700-8558National Hospital Organization Osaka National Hospital | Osaka , Japan, 540-0006Osaka International Cancer Institute | Osaka , Japan, 541-8567Hospital Angeles | Tijuana Estado de Baja California, Mexico, 22010Hospital Civil Fray Antonio Alcalde | Guadalajara Jalisco, Mexico, 44280Consultorio Dr. Reinoso | Monterrey Nuevo León, Mexico, 64320Centro de Atención E Investigación Clínica En Oncología | Mérida Yucatán, Mexico, 97134Centro de Alta Especialidad Reumatologia Inv del Potosi SC | San Luis Potosí City , Mexico, 78213Maastricht UMC+ | Maastricht Limburg, Netherlands, 6229 HXUniversity Medical Center Groningen | Groningen , Netherlands, 9713 GZLeids Universitair Medisch Centrum | Leiden , Netherlands, 2333 ZAUniversitair Medisch Centrum St Radboud Nijmegen | Nijmegen , Netherlands, 6525 GAErasmus Medisch Centrum | Rotterdam , Netherlands, 3015 GDNarodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy | Warsaw , Poland, 02-781Kazan Oncology Dispensary | Kazan' Tatarstan Republic, Russia, 420029Blokhin Cancer Research Center | Moscow , Russia, 115478St-Petersburg scientifical practical cente spec medical care | Saint Petersburg , Russia, 197758National Cancer Center | Goyang-si Gyeonggi-do, South Korea, 10408Asan Medical Center | Seoul Korea, South Korea, 05505Seoul St. Mary's Hospital | Seoul Korea, South Korea, 06591Severance Hospital, Yonsei University Health System | Seoul , South Korea, 03722Samsung Medical Center | Seoul , South Korea, 06351Hospital Universitario Virgen Del Rocio | Seville Andalusia, Spain, 41013Hospital Universitari Vall d'Hebron | Barcelona , Spain, 08035Hospital Duran I Reynals | Barcelona , Spain, 08907Hospital Clinico San Carlos | Madrid , Spain, 28040Hospital Universitario 12 de Octubre | Madrid , Spain, 28041Hospital Universitario La Fe de Valencia | Valencia , Spain, 46026Skånes universitetssjukhus Lund | Lund , Sweden, 22185Cantonal Hospital St.Gallen | Sankt Gallen Canton of St. Gallen, Switzerland, 9007Inselspital Bern | Bern , Switzerland, 3010National Taiwan University Hospital | Taipei , Taiwan, 10002Taipei Veterans General Hospital | Taipei , Taiwan, 11217Chang Gung Memorial Hospital - Linkou | Taoyuan Hsien , Taiwan, 333University College Hospital - London | London Greater London, United Kingdom, NW1 2BURoyal Marsden NHS Trust | London Greater London, United Kingdom, SW3 6JJThe Christie NHS Foundation Trust | Manchester Greater Manchester, United Kingdom, M20 4BXThe Clatterbridge Cancer Centre | Bebbington Merseyside, United Kingdom, CH63 4JYWeston Park Hospital | Sheffield South Yorkshire, United Kingdom, S10 2SJ
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
Study Documents (Full Text)
Documents provided by Eli Lilly and Company: Study Protocol: Study Protocol  January 28, 2015Documents provided by Eli Lilly and Company: Study Protocol: Study Protocol (d)  January 11, 2017Documents provided by Eli Lilly and Company: Statistical Analysis Plan  August 22, 2018