Clinical trial NCT02451943: A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Soft Tissue Sarcoma
Keywords: leiomyosarcoma
soft tissue sarcoma (STS)
advanced soft tissue sarcoma
metastatic soft tissue sarcoma
liposarcoma
undifferentiated pleomorphic sarcoma
doxorubicin
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-05-22
Enrollment: 509
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the efficacy of the combination of doxorubicin plus the study drug known as olaratumab versus doxorubicin plus placebo in participants with advanced or metastatic soft tissue sarcoma.


Eligibility criteria: 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).

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
measure: Overall Survival (OS) Leiomyosarcoma (LMS)
timeFrame: Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Randomization to Objective Progression or Death Due to Any Cause (Up to 35.8 Months)
measure: Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)
timeFrame: Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
measure: Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)
timeFrame: Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 45 Months)
measure: Time to First Worsening on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores
timeFrame: Randomization (Cycle 1) through Follow-up (Up to 35.8 Months)
measure: Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)
timeFrame: Randomization through Follow-up (Up to 35.8 Months)
measure: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
timeFrame: Randomization through Follow-up (Up to 34.5 Months)
measure: Duration of Overall Response (DoR)
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 33.4 Months)
measure: Duration of Disease Control (DDC)
timeFrame: Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)
measure: Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate
timeFrame: Cycle 1- 9: Day 1 and 8, Predose, 5 minutes Post dose and then every other cycle and follow-up (30 Days)
measure: PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate
timeFrame: Cycle 1- 9: Day 1 and 8; Predose, 5 Minutes Post dose and then every other cycle and follow-up (30 Days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists PC
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Cancer Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Fairfield
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Oncology Hematology Care Inc
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hematology Oncology, PC
state: Virginia
city: Caba
country: Argentina
facility: Alexander Fleming
state: BS
city: Caba
country: Argentina
facility: CENIT Centro de Neurociencias, Investigación y Tratamiento
state: Buenos Aires
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
state: Santa Fe
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Wien
country: Austria
facility: AKH
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
state: Brussel
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Rio de Janeiro
country: Brazil
facility: INCA Hospital do Câncer III
state: RJ
city: Sao Paulo
country: Brazil
facility: Icesp - Instituto Do Câncer Do Estado de São Paulo
state: São Paulo
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Vancouver
state: British Columbia
city: Lai Chi Kok
country: Canada
facility: Princess Margaret Hospital (Ontario)
state: Kowloon
city: Montreal
country: Canada
facility: Royal Victoria Hospital-Montreal
state: Quebec
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala
state: Pirkanmaa
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
city: Marseille CEDEX 05
country: France
facility: CHU Hopital d'enfants de la Timone
city: Paris
country: France
facility: Institut Curie
city: Toulouse cedex 9
country: France
facility: Institut Claudius Regaud
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Mannheim
country: Germany
facility: Klinikum Mannheim gGmbH Universitätsmedizin
state: Baden-Württemberg
city: Tubingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Munchen
country: Germany
facility: Klinikum der Universität München Großhadern
state: Bayern
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
state: Ramat Gan
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv Jaffa
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
state: Lombardie
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Catania
country: Italy
facility: Università degli Studi di Catania - Azienda Policlinico
state: Sicilia
city: Candiolo
country: Italy
facility: Istituto di Candiolo IRCCS - Fondazione del Piemonte per l'Oncologia
state: Torino
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
state: Saitama
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Japanese Foundation for Cancer Research
state: Tokyo
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
state: Korea
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Tijuana
country: Mexico
facility: Hospital Angeles
state: Baja California
city: Guadalajara
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
state: Jalisco
city: Monterrey
country: Mexico
facility: Consultorio Dr. Reinoso
state: Nuevo Leon
city: Merida
country: Mexico
facility: Centro de Atención E Investigación Clínica En Oncología
state: Yucatán
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad Reumatologia Inv del Potosi SC
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St Radboud Nijmegen
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
city: Kazan
country: Russian Federation
facility: Kazan Oncology Dispensary
state: Tatarstan Republic
city: Moscow
country: Russian Federation
facility: Blokhin Cancer Research Center
city: St. Petersburg
country: Russian Federation
facility: St-Petersburg scientifical practical cente spec medical care
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitario La Fe de Valencia
city: Lund
country: Sweden
facility: Skånes universitetssjukhus Lund
city: St Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen
state: Sankt Gallen
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan Hsien
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: London
country: United Kingdom
facility: University College Hospital - London
state: Greater London
city: London
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Greater London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: Bebbington
country: United Kingdom
facility: The Clatterbridge Cancer Centre
state: Merseyside
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: South Yorkshire
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.