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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02451943




Registration number
NCT02451943
Ethics application status
Date submitted
20/05/2015
Date registered
22/05/2015

Titles & IDs
Public title
A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma
Scientific title
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
Secondary ID [1] 0 0
I5B-MC-JGDJ
Secondary ID [2] 0 0
15677
Universal Trial Number (UTN)
Trial acronym
ANNOUNCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Soft Tissue Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Olaratumab
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: Olaratumab
Administered IV

Treatment: Drugs: Doxorubicin
Administered IV

Treatment: Drugs: Placebo
Administered IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Primary outcome [2] 0 0
Overall Survival (OS) Leiomyosarcoma (LMS)
Timepoint [2] 0 0
Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Secondary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Randomization to Objective Progression or Death Due to Any Cause (Up to 35.8 Months)
Secondary outcome [2] 0 0
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
Timepoint [2] 0 0
Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
Secondary outcome [3] 0 0
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
Timepoint [3] 0 0
Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 45 Months)
Secondary outcome [4] 0 0
Time to First Worsening on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores
Timepoint [4] 0 0
Randomization (Cycle 1) through Follow-up (Up to 35.8 Months)
Secondary outcome [5] 0 0
Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)
Timepoint [5] 0 0
Randomization through Follow-up (Up to 35.8 Months)
Secondary outcome [6] 0 0
Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
Timepoint [6] 0 0
Randomization through Follow-up (Up to 34.5 Months)
Secondary outcome [7] 0 0
Duration of Overall Response (DoR)
Timepoint [7] 0 0
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 33.4 Months)
Secondary outcome [8] 0 0
Duration of Disease Control (DDC)
Timepoint [8] 0 0
Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
Secondary outcome [9] 0 0
Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate
Timepoint [9] 0 0
Cycle 1- 9: Day 1 and 8, Predose, 5 minutes Post dose and then every other cycle and follow-up (30 Days)
Secondary outcome [10] 0 0
PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate
Timepoint [10] 0 0
Cycle 1- 9: Day 1 and 8; Predose, 5 Minutes Post dose and then every other cycle and follow-up (30 Days)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
Accrual to date
Final
509
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New Mexico
Country [10] 0 0
United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Oregon
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Pennsylvania
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Tennessee
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United States of America
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Utah
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United States of America
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Virginia
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Argentina
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BS
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Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Argentina
State/province [20] 0 0
Santa Fe
Country [21] 0 0
Austria
State/province [21] 0 0
Wien
Country [22] 0 0
Belgium
State/province [22] 0 0
Brussel
Country [23] 0 0
Belgium
State/province [23] 0 0
Oost-Vlaanderen
Country [24] 0 0
Belgium
State/province [24] 0 0
Leuven
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Brazil
State/province [25] 0 0
RJ
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Brazil
State/province [26] 0 0
São Paulo
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
Kowloon
Country [30] 0 0
Canada
State/province [30] 0 0
Quebec
Country [31] 0 0
Denmark
State/province [31] 0 0
Herlev
Country [32] 0 0
Finland
State/province [32] 0 0
Pirkanmaa
Country [33] 0 0
Finland
State/province [33] 0 0
Turku
Country [34] 0 0
France
State/province [34] 0 0
Côte-d'Or
Country [35] 0 0
France
State/province [35] 0 0
Rhône-Alpes
Country [36] 0 0
France
State/province [36] 0 0
Bordeaux
Country [37] 0 0
France
State/province [37] 0 0
Marseille CEDEX 05
Country [38] 0 0
France
State/province [38] 0 0
Paris
Country [39] 0 0
France
State/province [39] 0 0
Toulouse cedex 9
Country [40] 0 0
France
State/province [40] 0 0
Villejuif Cedex
Country [41] 0 0
Germany
State/province [41] 0 0
Baden-Württemberg
Country [42] 0 0
Germany
State/province [42] 0 0
Bayern
Country [43] 0 0
Germany
State/province [43] 0 0
Nordrhein-Westfalen
Country [44] 0 0
Germany
State/province [44] 0 0
Berlin
Country [45] 0 0
Hungary
State/province [45] 0 0
Budapest
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Israel
State/province [46] 0 0
Ramat Gan
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Israel
State/province [47] 0 0
Jerusalem
Country [48] 0 0
Israel
State/province [48] 0 0
Tel Aviv Jaffa
Country [49] 0 0
Italy
State/province [49] 0 0
Lombardie
Country [50] 0 0
Italy
State/province [50] 0 0
Milano
Country [51] 0 0
Italy
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Sicilia
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Italy
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Torino
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Japan
State/province [53] 0 0
Aichi
Country [54] 0 0
Japan
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Chiba
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Japan
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Hokkaido
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Japan
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Osaka
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Japan
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Saitama
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Japan
State/province [58] 0 0
Tokyo
Country [59] 0 0
Japan
State/province [59] 0 0
Fukuoka
Country [60] 0 0
Japan
State/province [60] 0 0
Okayama
Country [61] 0 0
Korea, Republic of
State/province [61] 0 0
Gyeonggi-do
Country [62] 0 0
Korea, Republic of
State/province [62] 0 0
Korea
Country [63] 0 0
Korea, Republic of
State/province [63] 0 0
Seoul
Country [64] 0 0
Mexico
State/province [64] 0 0
Baja California
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Mexico
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Jalisco
Country [66] 0 0
Mexico
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Nuevo Leon
Country [67] 0 0
Mexico
State/province [67] 0 0
Yucatán
Country [68] 0 0
Mexico
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San Luis Potosi
Country [69] 0 0
Netherlands
State/province [69] 0 0
Limburg
Country [70] 0 0
Netherlands
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Groningen
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Netherlands
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Leiden
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Netherlands
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Nijmegen
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Netherlands
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Rotterdam
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Poland
State/province [74] 0 0
Warszawa
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Tatarstan Republic
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Moscow
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Russian Federation
State/province [77] 0 0
St. Petersburg
Country [78] 0 0
Spain
State/province [78] 0 0
Andalucía
Country [79] 0 0
Spain
State/province [79] 0 0
Barcelona
Country [80] 0 0
Spain
State/province [80] 0 0
Madrid
Country [81] 0 0
Spain
State/province [81] 0 0
Valencia
Country [82] 0 0
Sweden
State/province [82] 0 0
Lund
Country [83] 0 0
Switzerland
State/province [83] 0 0
Sankt Gallen
Country [84] 0 0
Switzerland
State/province [84] 0 0
Bern
Country [85] 0 0
Taiwan
State/province [85] 0 0
Taipei City
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taipei
Country [87] 0 0
Taiwan
State/province [87] 0 0
Taoyuan Hsien
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Greater London
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Greater Manchester
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Merseyside
Country [91] 0 0
United Kingdom
State/province [91] 0 0
South Yorkshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02451943