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A Study of Olaratumab in Soft Tissue Sarcoma

Primary Purpose

Sarcoma, Soft Tissue

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Olaratumab
doxorubicin
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma, Soft Tissue focused on measuring Sarcoma, Soft Tissue, Advanced Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • The participant has histologically- or cytologically-confirmed malignant soft tissue sarcoma
  • The participant has advanced soft tissue sarcoma (STS), not amenable to treatment with surgery or radiotherapy
  • The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-2
  • The participant has available tumor tissue from either the primary or metastatic tumor for determination of PDGFRα expression
  • The participant has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500 μL, hemoglobin ≥ 9.0 g/dL, and a platelet count of 100,000/μL obtained within 2 weeks prior to study entry
  • The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN)
  • The participant has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45 mL/min
  • Because the teratogenicity of Olaratumab is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

Exclusion Criteria:

  • The participant has histologically- or cytologically-confirmed Kaposi's sarcoma
  • The participant has untreated central nervous system metastases
  • The participant received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (ie, mitoxantrone)
  • The participant received prior radiation therapy to the mediastinal/pericardial area
  • The participant has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to study entry
  • The participant is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent
  • The participant has an elective or a planned major surgery to be performed during the course of the study
  • The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, requiring parenteral antibiotics, symptomatic congestive heart failure, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry
  • The participant has known immunodeficiency virus (HIV) infection
  • The participant, if female, is pregnant or lactating
  • The participant has a known allergy to any of the treatment components

Sites / Locations

  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Phase 1b: Olaratumab + doxorubicin

Phase 2: Olaratumab and doxorubicin

Phase 2: Doxorubicin: Optional Olaratumab After Progression

Arm Description

All cycles are 21 days. Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1 All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8

All cycles are 21 days. Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1 All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8

All cycles are 21 days. Cycles 1-8: doxorubicin 75 mg/m2 on day 1 until disease progression. At disease progression: optional Olaratumab 15 mg/kg on days 1+8 until further progression.

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
PFS is measured from randomization until the first radiographic documentation of progression of disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause. Participants who died without PD was considered to have progressed on the day of death. The following censoring rules applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization. Participants were censored at the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last adequate radiographic visit. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study
All Phase 1b participants who experienced at least 1 TEAE in the Phase 1b portion of the study. Adverse Event with missing relationship to study is counted as related. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.

Secondary Outcome Measures

Number of Participants With AEs and SAEs for Phase 2 Portion
A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Overall Survival (OS)
OS was defined as the date of randomization to the date of death from any cause. Reasons for censoring OS were that participant was known to be alive, participant was lost to follow up during the study or participant withdrew consent to follow up.
Percentage of Participants With Objective Response (Objective Response Rate)
Objective Response Rate (ORR) is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.
Percentage of Participants Who Are Progression-Free (PFS) at 3 Months
(PFS) rate is defined as the percentage of participants that are alive and progression-free 3 months after randomization. PFS is measured from randomization until the first radiographic progressive disease as defined by RECIST (version 1.1) or death from any cause. Participants who died without PD were considered to have progressed on the day of death. Censoring applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization or the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit. If participant started new treatment before PD, participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab
PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
AUCτ = area under the concentration versus time curve during one dosing interval with a measurable concentration.
PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
Percentage of Participants With Anti-Olaratumab Antibody Assessment
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

Full Information

First Posted
August 19, 2010
Last Updated
March 3, 2017
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT01185964
Brief Title
A Study of Olaratumab in Soft Tissue Sarcoma
Official Title
A Phase 1b/2, With Phase 2 Randomized, Study Evaluating the Efficacy of Doxorubicin With or Without a Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) in the Treatment of Advanced Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The main purpose of this study is to gather information about the use of an investigational drug called olaratumab with a drug for soft tissue sarcoma called doxorubicin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Soft Tissue
Keywords
Sarcoma, Soft Tissue, Advanced Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
148 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b: Olaratumab + doxorubicin
Arm Type
Experimental
Arm Description
All cycles are 21 days. Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1 All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8
Arm Title
Phase 2: Olaratumab and doxorubicin
Arm Type
Experimental
Arm Description
All cycles are 21 days. Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1 All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8
Arm Title
Phase 2: Doxorubicin: Optional Olaratumab After Progression
Arm Type
Active Comparator
Arm Description
All cycles are 21 days. Cycles 1-8: doxorubicin 75 mg/m2 on day 1 until disease progression. At disease progression: optional Olaratumab 15 mg/kg on days 1+8 until further progression.
Intervention Type
Biological
Intervention Name(s)
Olaratumab
Other Intervention Name(s)
LY3012207, IMC-3G3
Intervention Description
Olaratumab 15 mg/kg by intravenous transfusion (I.V.) on days 1+8 of a 21-day cycle
Intervention Type
Drug
Intervention Name(s)
doxorubicin
Intervention Description
Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
PFS is measured from randomization until the first radiographic documentation of progression of disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause. Participants who died without PD was considered to have progressed on the day of death. The following censoring rules applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization. Participants were censored at the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last adequate radiographic visit. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Time Frame
Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months)
Title
Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study
Description
All Phase 1b participants who experienced at least 1 TEAE in the Phase 1b portion of the study. Adverse Event with missing relationship to study is counted as related. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time Frame
Baseline Up to 30 Months
Secondary Outcome Measure Information:
Title
Number of Participants With AEs and SAEs for Phase 2 Portion
Description
A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time Frame
Baseline, Up to 30 Months
Title
Overall Survival (OS)
Description
OS was defined as the date of randomization to the date of death from any cause. Reasons for censoring OS were that participant was known to be alive, participant was lost to follow up during the study or participant withdrew consent to follow up.
Time Frame
Randomization to the Date of Death From Any Cause (Up To 47 Months)
Title
Percentage of Participants With Objective Response (Objective Response Rate)
Description
Objective Response Rate (ORR) is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.
Time Frame
Randomization Until Progressive Disease (Up to 30 Months)
Title
Percentage of Participants Who Are Progression-Free (PFS) at 3 Months
Description
(PFS) rate is defined as the percentage of participants that are alive and progression-free 3 months after randomization. PFS is measured from randomization until the first radiographic progressive disease as defined by RECIST (version 1.1) or death from any cause. Participants who died without PD were considered to have progressed on the day of death. Censoring applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization or the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit. If participant started new treatment before PD, participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
Time Frame
Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months)
Title
Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab
Time Frame
Cycle 1 Day 1: Preinfusion, End of Infusion,1hr,48hr,72hr,168 hr Post infusion; Cycle 3 Day 1:Preinfusion, End of Infusion,1hr,24hr,48hr,72hr,168hr Post Infusion
Title
PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
Time Frame
Cycle 1 Day 8: Preinfusion, 1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr, 24hr,72hr,168hr Post Infusion
Title
PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
Description
AUCτ = area under the concentration versus time curve during one dosing interval with a measurable concentration.
Time Frame
Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion
Title
PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
Time Frame
Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion
Title
Percentage of Participants With Anti-Olaratumab Antibody Assessment
Description
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time Frame
Baseline, Up to 30 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The participant has histologically- or cytologically-confirmed malignant soft tissue sarcoma The participant has advanced soft tissue sarcoma (STS), not amenable to treatment with surgery or radiotherapy The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-2 The participant has available tumor tissue from either the primary or metastatic tumor for determination of PDGFRα expression The participant has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500 μL, hemoglobin ≥ 9.0 g/dL, and a platelet count of 100,000/μL obtained within 2 weeks prior to study entry The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN) The participant has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45 mL/min Because the teratogenicity of Olaratumab is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Exclusion Criteria: The participant has histologically- or cytologically-confirmed Kaposi's sarcoma The participant has untreated central nervous system metastases The participant received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (ie, mitoxantrone) The participant received prior radiation therapy to the mediastinal/pericardial area The participant has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to study entry The participant is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent The participant has an elective or a planned major surgery to be performed during the course of the study The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, requiring parenteral antibiotics, symptomatic congestive heart failure, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry The participant has known immunodeficiency virus (HIV) infection The participant, if female, is pregnant or lactating The participant has a known allergy to any of the treatment components
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
ImClone Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
ImClone Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
ImClone Investigational Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
ImClone Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
ImClone Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
ImClone Investigational Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
ImClone Investigational Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
ImClone Investigational Site
City
St Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
ImClone Investigational Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
ImClone Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
ImClone Investigational Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
ImClone Investigational Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
ImClone Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
ImClone Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
ImClone Investigational Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27291997
Citation
Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. doi: 10.1016/S0140-6736(16)30587-6. Epub 2016 Jun 9. Erratum In: Lancet. 2016 Jul 30;388(10043):464.
Results Reference
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A Study of Olaratumab in Soft Tissue Sarcoma

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