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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02451943
First received: May 20, 2015
Last updated: August 1, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Soft Tissue Sarcoma
Drug: Olaratumab
Drug: Doxorubicin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Randomization to Date of Death Due to Any Cause (Estimated Up to 45 Months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Randomization to Objective Progression or Death Due to Any Cause (Estimated Up to 45 Months) ] [ Designated as safety issue: No ]
  • Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [ Time Frame: Randomization to Objective Disease Progression or Death Due to Any Cause (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Percentage of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [ Time Frame: Randomization to Objective Disease Progression or Death Due to Any Cause (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Scores [ Time Frame: Randomization through Follow-up (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) [ Time Frame: Randomization through Follow-up (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score" [ Time Frame: Randomization through Follow-up (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Duration of Disease Control (DDC) [ Time Frame: Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Estimated up to 45 Months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Minimum Concentration (Cmin) Prior to 4th cycle of Olaratumab [ Time Frame: Pre-dose Day 1 of Cycle 4 (21 Day Cycles) ] [ Designated as safety issue: No ]

Estimated Enrollment: 460
Study Start Date: September 2015
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxorubicin + Olaratumab
75 milligrams per meter squared (mg/m^2) doxorubicin administered intravenously (IV) on day 1 of each 21 day cycle for 8 cycles plus 20 milligrams per kilogram (mg/kg) dose of olaratumab administered IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab administered IV on day 1 and day 8 of cycles 2-8. Beginning with cycle 9, 15 mg/kg olaratumab administered IV on day 1 and day 8 of each subsequent 21 day cycle until documented progressive disease (PD) or discontinuation for any other reason.
Drug: Olaratumab
Administered IV
Other Name: LY3012207
Drug: Doxorubicin
Administered IV
Placebo Comparator: Doxorubicin + Placebo
75 mg/m^2 doxorubicin administered IV on day 1 of each 21 day cycle for 8 cycles plus placebo (equivalent volume) administered IV on day 1 and day 8 for 8 cycles. Beginning with cycle 9, placebo (equivalent volume) administered on days 1 and 8 of each subsequent 21 day cycle until PD or discontinuation for any other reason.
Drug: Doxorubicin
Administered IV
Drug: Placebo
Administered IV

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02451943

  Show 118 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02451943     History of Changes
Other Study ID Numbers: 15677  I5B-MC-JGDJ  2015‐000134‐30 
Study First Received: May 20, 2015
Last Updated: August 1, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Austrian Medicines and Medical Devices Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada
Denmark: Danish Health and Medicines Authority
Finland: Finnish Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: The Italian Medicines Agency
Japan: Ministry of Health, Labor and Welfare
South Korea: Ministry of Food and Drug Safety
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan : Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Japan: Pharmaceuticals and Medical Devices Agency
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.


Keywords provided by Eli Lilly and Company:
leiomyosarcoma
soft tissue sarcoma (STS)
advanced soft tissue sarcoma
metastatic soft tissue sarcoma
liposarcoma
undifferentiated pleomorphic sarcoma
doxorubicin

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 25, 2016