Back to resultsA Study of Olaratumab (LY3012207) in Participants With Soft Tissue Sarcoma
Primary Purpose
Soft Tissue Sarcoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Olaratumab
Doxorubicin
External Beam Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Soft Tissue Sarcoma
Eligibility Criteria
Inclusion Criteria:
- Have a histologically confirmed diagnosis of STS for which olaratumab and doxorubicin would be appropriate therapy. Participants with a diagnosis of Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Participants must have potentially resectable disease (as assessed by the study investigator) and have a primary tumor lesion deemed amenable to serial biopsy.
- For radiotherapy addendum only: Have a histologically confirmed diagnosis of STS of the extremities, Grade 2 or 3, >5 centimeters, for which olaratumab and radiotherapy would be appropriate therapy. Participants with Kaposi's sarcoma, GIST or myxoid liposarcoma will be excluded.
- Have consented to undergo mandatory serial peripheral whole blood and tumor tissue sampling.
Exclusion Criteria:
- Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. 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 enrollment to rule out brain metastasis.
- Have received 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.
- For radiotherapy addendum only: Have received previous radiotherapy in the primary tumor lesion and/or prior treatment with olaratumab or has participated in a prior olaratumab trial.
Sites / Locations
- USC/Norris Comp Cancer Center
- Yale University School of Medicine
- All Children's Hospital
- Moffitt Cancer Center & Research Inst
- Kansas City Cancer Center
- Washington University Medical Center
- Levine Children's Hospital
- Vanderbilt University Medical Center
- Mary Crowley Cancer Research
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Olaratumab + Doxorubicin
Olaratumab + Radiotherapy Addendum
Arm Description
Cycle 1: Olaratumab 20 milligram per kilogram (mg/kg) given intravenously (IV) on Day 1 and Day 8 (21 day cycle). Cycle 2: Olaratumab 20 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycle). Cycle 3 through Cycle 7: Olaratumab 15 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycles).
Olaratumab given IV on Day 1 and Day 8 (21 day cycle) concurrently with radiotherapy. Radiotherapy addendum was not implemented.
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood
Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.
Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue
Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.
Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue
PDGF A, PDGF B, PDGF C, and PDGF D are platelet-derived growth factor canonical ligands associated with activation of PDGFR α and β.
Secondary Outcome Measures
Progression Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the date of first study dose to the first date of radiologic disease progression or death due to any cause. Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)
Overall Response Rate (ORR) is defined as the percentage of participants achieving a best overall response of either Complete Response (CR) or Partial Response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to <10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response from the start of the treatment until progressive disease (PD)/recurrence.
Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR
Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to <10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD.
Participants who do not have any post-baseline tumor response assessments for any reason are considered non-responders and are included in the denominator when calculating the response rate.
Percentage of Participants With Resectable Tumors (Resectability Rate)
Resectability rate is obtained when the total number of participants with resectable tumors is divided by the total number of participants. Resectability of a tumor is determined by the surgeon and multi-disciplinary team and dependent on tumor stage and the participants coexisting medical conditions.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy
Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab
Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.
Number of Participants With Anti-Olaratumab Antibodies
A participant is counted as positive if they had at least one anti-olaratumab antibody positive result during the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02783599
Brief Title
A Study of Olaratumab (LY3012207) in Participants With Soft Tissue Sarcoma
Official Title
A Phase 1b Trial to Assess the Modulation of Biological Markers in Patients With Potentially Resectable Soft Tissue Sarcoma Treated With Olaratumab Monotherapy Followed by Olaratumab Plus Doxorubicin Combination Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
October 11, 2016 (Actual)
Primary Completion Date
July 5, 2018 (Actual)
Study Completion Date
July 5, 2018 (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 purpose of this study is to evaluate potential biomarkers and method of action, efficacy and safety of olaratumab in participants with soft tissue sarcoma (STS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Olaratumab + Doxorubicin
Arm Type
Experimental
Arm Description
Cycle 1: Olaratumab 20 milligram per kilogram (mg/kg) given intravenously (IV) on Day 1 and Day 8 (21 day cycle).
Cycle 2: Olaratumab 20 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycle).
Cycle 3 through Cycle 7: Olaratumab 15 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycles).
Arm Title
Olaratumab + Radiotherapy Addendum
Arm Type
Experimental
Arm Description
Olaratumab given IV on Day 1 and Day 8 (21 day cycle) concurrently with radiotherapy.
Radiotherapy addendum was not implemented.
Intervention Type
Drug
Intervention Name(s)
Olaratumab
Other Intervention Name(s)
LY3012207
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Administered IV
Intervention Type
Radiation
Intervention Name(s)
External Beam Radiotherapy
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood
Description
Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.
Time Frame
Baseline, End of Cycle 1 (21 days)
Title
Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue
Description
Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.
Time Frame
Baseline, End of Cycle 1 (21 days)
Title
Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue
Description
PDGF A, PDGF B, PDGF C, and PDGF D are platelet-derived growth factor canonical ligands associated with activation of PDGFR α and β.
Time Frame
Baseline, End of Cycle 1 (21 days)
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
Progression-free survival (PFS) is defined as the time from the date of first study dose to the first date of radiologic disease progression or death due to any cause. Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Time Frame
Baseline to Objective Progression or Death from Any Cause (Up to 18 Months)
Title
Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)
Description
Overall Response Rate (ORR) is defined as the percentage of participants achieving a best overall response of either Complete Response (CR) or Partial Response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to <10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response from the start of the treatment until progressive disease (PD)/recurrence.
Time Frame
Baseline to Measured Progressive Disease (Up to 18 Months)
Title
Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR
Description
Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to <10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD.
Participants who do not have any post-baseline tumor response assessments for any reason are considered non-responders and are included in the denominator when calculating the response rate.
Time Frame
Baseline to Measured Progressive Disease (Up to 18 Months)
Title
Percentage of Participants With Resectable Tumors (Resectability Rate)
Description
Resectability rate is obtained when the total number of participants with resectable tumors is divided by the total number of participants. Resectability of a tumor is determined by the surgeon and multi-disciplinary team and dependent on tumor stage and the participants coexisting medical conditions.
Time Frame
Cycle 1 through Cycle 7 (Up to 6 Months)
Title
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy
Description
Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8
Time Frame
Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion
Title
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab
Description
Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.
Time Frame
Cycle 2 Day 1: Predose, 5 minutes(m) post-infusion, 24 hours(h), 96h; Day 8:Predose, 5 m, and 24h, 48h, 96h, and 240h postdose; Cycle 3 Day 1 and Day 8: Predose and 5m post-infusion
Title
Number of Participants With Anti-Olaratumab Antibodies
Description
A participant is counted as positive if they had at least one anti-olaratumab antibody positive result during the study.
Time Frame
Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have a histologically confirmed diagnosis of STS for which olaratumab and doxorubicin would be appropriate therapy. Participants with a diagnosis of Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. Participants with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Participants must have potentially resectable disease (as assessed by the study investigator) and have a primary tumor lesion deemed amenable to serial biopsy.
For radiotherapy addendum only: Have a histologically confirmed diagnosis of STS of the extremities, Grade 2 or 3, >5 centimeters, for which olaratumab and radiotherapy would be appropriate therapy. Participants with Kaposi's sarcoma, GIST or myxoid liposarcoma will be excluded.
Have consented to undergo mandatory serial peripheral whole blood and tumor tissue sampling.
Exclusion Criteria:
Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. 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 enrollment to rule out brain metastasis.
Have received 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.
For radiotherapy addendum only: Have received previous radiotherapy in the primary tumor lesion and/or prior treatment with olaratumab or has participated in a prior olaratumab trial.
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
USC/Norris Comp Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Moffitt Cancer Center & Research Inst
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Kansas City Cancer Center
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
Washington University Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Mary Crowley Cancer Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Olaratumab (LY3012207) in Participants With Soft Tissue Sarcoma
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