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CompletedNCT02451943ANNOUNCEUpdated Jul 15, 2025Results posted

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

A Phase 3 interventional study of Olaratumab and Doxorubicin in Soft Tissue Sarcoma, sponsored by Eli Lilly and Company. Completed at 114 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-15.

Sponsored by Eli Lilly and Company · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
509
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Soft Tissue Sarcoma

Keywords

  • leiomyosarcoma
  • soft tissue sarcoma (STS)
  • advanced soft tissue sarcoma
  • metastatic soft tissue sarcoma
  • liposarcoma
  • undifferentiated pleomorphic sarcoma
  • doxorubicin
03

In context

Sarcoma

1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.

This study's enrollment of 509 is above the median of 40 across 1,283 interventional studies indexed under Sarcoma.

Browse Sarcoma studies →

Lead sponsor

Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.

Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
509 participants (actual)

Study arms

  • 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 · Drug: Doxorubicin

  • 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: Doxorubicin · Drug: Placebo

Interventions

  • DrugOlaratumab

    Administered IV

    Also known as: LY3012207

  • DrugDoxorubicin

    Administered IV

  • DrugPlacebo

    Administered IV

06

What researchers measure

Primary outcomes

  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.

    Time frame: Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)

  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.

    Time frame: Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)

Secondary outcomes

  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.

    Time frame: Randomization to Objective Progression or Death Due to Any Cause (Up to 35.8 Months)

  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.

    Time frame: Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)

  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.

    Time frame: Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.5 Months)

  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.

    Time frame: Randomization (Cycle 1) through Follow-up (Up to 35.8 Months)

  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.

    Time frame: Randomization through Follow-up (Up to 35.8 Months)

  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).

    Time frame: Randomization through Follow-up (Up to 34.5 Months)

  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).

    Time frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 33.4 Months)

  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.

    Time frame: Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)

  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.

    Time frame: Cycle 1- 9: Day 1 and 8, Predose, 5 minutes Post dose and then every other cycle and follow-up (30 Days)

  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).

    Time frame: Cycle 1- 9: Day 1 and 8; Predose, 5 Minutes Post dose and then every other cycle and follow-up (30 Days)

07

Results

Posted Dec 17, 2019

Participant flow

Participant flow — Overall Study
MilestoneDoxorubicin + OlaratumabDoxorubicin + Placebo
Started258251
Received at least one dose of study drug257249
Completed242227
Not completed1624
Withdrew: Withdrawal by subject1316
Withdrew: Lost to follow-up34
Withdrew: Sponsor decision04

Outcome measures

PrimaryOverall 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.

Time frame:
Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Reported as:
Median · Months
Overall Survival (OS)
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Overall Survival (OS)20.37 (17.84 to 22.90)19.75 (16.49 to 23.75)
Statistical analysis
  • Doxorubicin + Olaratumab vs Doxorubicin + Placebo · Log Rank · p = 0.6945 · Hazard ratio (hr): 1.047 · 95% CI 0.841 to 1.303Stratified
PrimaryOverall 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.

Time frame:
Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Reported as:
Median · Months
Overall Survival (OS) Leiomyosarcoma (LMS)
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Overall Survival (OS) Leiomyosarcoma (LMS)21.55 (18.63 to 27.63)21.88 (17.54 to 25.07)
Statistical analysis
  • Doxorubicin + Olaratumab vs Doxorubicin + Placebo · Log Rank · p = 0.7618 · Hazard ratio (hr): 0.951 · 95% CI 0.690 to 1.312Stratified
SecondaryProgression 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.

Time frame:
Randomization to Objective Progression or Death Due to Any Cause (Up to 35.8 Months)
Reported as:
Median · Months
Progression Free Survival (PFS)
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Progression Free Survival (PFS)5.42 (4.11 to 6.70)6.77 (5.49 to 8.08)
Statistical analysis
  • Doxorubicin + Olaratumab vs Doxorubicin + Placebo · Log Rank · p = 0.0422 · Hazard ratio (hr): 1.231 · 95% CI 1.009 to 1.502Stratified
SecondaryPercentage 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.

Time frame:
Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
Reported as:
Number · percentage of participants
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
percentage of participantsDoxorubicin + OlaratumabDoxorubicin + Placebo
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)14.0 (9.7 to 18.2)18.3 (13.5 to 23.1)
SecondaryPercentage 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.

Time frame:
Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.5 Months)
Reported as:
Number · percentage of participants
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
percentage of participantsDoxorubicin + OlaratumabDoxorubicin + Placebo
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)67.4 (61.7 to 73.2)75.7 (70.4 to 81.0)
SecondaryTime 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.

Time frame:
Randomization (Cycle 1) through Follow-up (Up to 35.8 Months)
Reported as:
Median · 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
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Global Health Status/QoL1.45 (1.41 to 2.10)1.84 (1.45 to 2.79)
Role Functional Scale1.41 (0.99 to 1.48)1.41 (0.95 to 2.00)
Physical Functional Scale1.81 (1.45 to 2.14)2.79 (2.07 to 3.48)
Emotional Functional Scale3.48 (2.50 to 4.37)2.83 (2.14 to 4.34)
Cognitive Functional Scale1.64 (1.41 to 2.14)1.45 (1.41 to 2.07)
Social Functional Scale1.45 (1.38 to 1.64)1.41 (1.35 to 1.45)
Fatigue Symptom Scale0.92 (0.76 to 1.25)0.89 (0.76 to 1.38)
Nausea and Vomiting Symptom Scale1.45 (1.41 to 1.64)1.41 (0.95 to 1.45)
Pain Symptom Scale1.64 (1.41 to 2.10)2.10 (1.45 to 2.76)
Dyspnea Symptom Scale2.10 (1.45 to 2.76)2.07 (1.45 to 2.79)
Insomnia Symptom Scale2.10 (1.45 to 2.79)1.58 (1.41 to 2.33)
Appetite Loss Symptom Scale1.48 (1.45 to 2.04)1.64 (1.41 to 2.14)
Financial Difficulties Scale1.48 (1.41 to 2.14)1.45 (1.41 to 2.10)
Constipation Symptom Scale1.64 (1.41 to 2.10)1.41 (1.41 to 2.10)
Diarrhea Symptom Scale2.07 (1.45 to 2.79)2.79 (2.10 to 3.52)
SecondaryChange 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.

Time frame:
Randomization through Follow-up (Up to 35.8 Months)
Reported as:
Mean · score on a scale
Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)
score on a scaleDoxorubicin + OlaratumabDoxorubicin + Placebo
Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)-0.163 ± 0.236-0.171 ± 0.235
SecondaryTime 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).

Time frame:
Randomization through Follow-up (Up to 34.5 Months)
Reported as:
Median · Months
Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"7.66 (6.01 to 9.63)8.08 (6.18 to 11.07)
SecondaryDuration 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).

Time frame:
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 33.4 Months)
Reported as:
Median · Months
Duration of Overall Response (DoR)
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Duration of Overall Response (DoR)8.31 (6.87 to 12.35)4.80 (3.65 to 6.83)
Statistical analysis
  • Doxorubicin + Olaratumab vs Doxorubicin + Placebo · Log Rank · p = 0.0934 · Hazard ratio (hr): 0.616 · 95% CI 0.347 to 1.093Stratified
SecondaryDuration 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.

Time frame:
Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
Reported as:
Median · Months
Duration of Disease Control (DDC)
MonthsDoxorubicin + OlaratumabDoxorubicin + Placebo
Duration of Disease Control (DDC)8.28 (6.93 to 9.72)8.34 (8.08 to 9.46)
Statistical analysis
  • Doxorubicin + Olaratumab vs Doxorubicin + Placebo · Log Rank · p = 0.3347 · Hazard ratio (hr): 1.123 · 95% CI 0.892 to 1.413Stratified
SecondaryPharmacokinetics (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.

Time frame:
Cycle 1- 9: Day 1 and 8, Predose, 5 minutes Post dose and then every other cycle and follow-up (30 Days)
Reported as:
Mean · Liter/hour (L/h)
Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate
Liter/hour (L/h)Doxorubicin + Olaratumab
Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate0.0195 (0.0189 to 0.0203)
SecondaryPK: 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).

Time frame:
Cycle 1- 9: Day 1 and 8; Predose, 5 Minutes Post dose and then every other cycle and follow-up (30 Days)
Reported as:
Mean · Liter (L)
PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate
Liter (L)Doxorubicin + Olaratumab
PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate5.72 (5.28 to 6.17)

Adverse events

Collected over Baseline Up To 41 Months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Doxorubicin + Olaratumab170/257 (66.1%)105/257 (40.9%)248/257 (96.5%)
Doxorubicin + Placebo158/249 (63.5%)89/249 (35.7%)244/249 (98%)
Most frequent serious events
Showing 10 of 123
Most frequent serious events
EventDoxorubicin + OlaratumabDoxorubicin + Placebo
Febrile neutropeniaBlood and lymphatic system disorders34/25733/249
NeutropeniaBlood and lymphatic system disorders8/2578/249
PyrexiaGeneral disorders2/2577/249
Pulmonary embolismRespiratory, thoracic and mediastinal disorders7/2573/249
Neutrophil count decreasedInvestigations5/2574/249
Deep vein thrombosisVascular disorders5/2571/249
AnaemiaBlood and lymphatic system disorders4/2572/249
NauseaGastrointestinal disorders4/2570/249
VomitingGastrointestinal disorders4/2571/249
PneumoniaInfections and infestations4/2572/249
Most frequent other events
Showing 10 of 56
Most frequent other events
EventDoxorubicin + OlaratumabDoxorubicin + Placebo
NauseaGastrointestinal disorders154/257171/249
FatigueGeneral disorders129/257133/249
AlopeciaSkin and subcutaneous tissue disorders113/257127/249
AnaemiaBlood and lymphatic system disorders115/257121/249
ConstipationGastrointestinal disorders86/25794/249
StomatitisGastrointestinal disorders79/25793/249
Decreased appetiteMetabolism and nutrition disorders74/25793/249
Neutrophil count decreasedInvestigations92/25790/249
DiarrhoeaGastrointestinal disorders79/25776/249
VomitingGastrointestinal disorders62/25770/249

Baseline characteristics

All randomized participants.

Age, Continuous
Age, Continuous(years)Doxorubicin + OlaratumabDoxorubicin + PlaceboTotal
Mean56.7 ± 12.457.1 ± 11.656.9 ± 12.0
Sex: Female, Male
Sex: Female, Male(Participants)Doxorubicin + OlaratumabDoxorubicin + PlaceboTotal
Female144152296
Male11499213
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Doxorubicin + OlaratumabDoxorubicin + PlaceboTotal
Hispanic or Latino262955
Not Hispanic or Latino209199408
Unknown or Not Reported232346
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Doxorubicin + OlaratumabDoxorubicin + PlaceboTotal
American Indian or Alaska Native336
Asian504898
Native Hawaiian or Other Pacific Islander101
Black or African American12214
White186193379
More than one race549
Unknown or Not Reported112
Region of Enrollment
Region of Enrollment(Participants)Doxorubicin + OlaratumabDoxorubicin + PlaceboTotal
United States6973142
Russia7815
Austria303
South Korea151328
Netherlands8614
Sweden437
Brazil202
Poland325
France171835
Argentina347
Hungary91120
Japan232245
United Kingdom101626
Switzerland426
Spain132134
Canada12618
Belgium111021
Finland426
Taiwan6713
Denmark10212
Italy549
Mexico7613
Israel6511
Australia011
Germany7916
08

Study locations

114 sites
  • 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

Showing the first 100 of 114 sites across 25 countries.

09

References and documents

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. PubMed 33632930 ↗
  • 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. PubMed 32259228 ↗
  • 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. PubMed 28447475 ↗

Study documents

  • Study protocol · Jan 29, 2015
  • Study protocol · Jan 12, 2017
  • Statistical analysis plan · Aug 23, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 15, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02451943
Lead sponsor
Eli Lilly and Company
Responsible party
Sponsor
First posted
May 22, 2015
Start date
Sep 14, 2015
Primary completion
Dec 5, 2018
Completion
Jun 27, 2024
Results posted
Dec 17, 2019
Last update
Jul 15, 2025

Study contacts

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)
study director · Eli Lilly and Company

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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