A Study of Olaratumab (LY3012207) in Participants With Soft Tissue Sarcoma

Soft Tissue Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02783599
• Other study ID #: 15840
• Secondary ID: I5B-MC-JGDM2015-
• Status: Completed
• Phase: Phase 1
• Start date: October 11, 2016
• Est. completion date: July 5, 2018

Study information

• Verified date: February 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: July 5, 2018
• Est. primary completion date: July 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• Olaratumab
Administered IV
• Doxorubicin
Administered IV

Radiation:
• External Beam Radiotherapy

Locations

Country	Name	City	State
France	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.	Lyon
Italy	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.	Milano
Spain	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.	Barcelona
Spain	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.	Sevilla
United Kingdom	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.	London
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	USC/Norris Comp Cancer Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Kansas City Cancer Center	Overland Park	Kansas
United States	Washington University Medical Center	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Moffitt Cancer Center & Research Inst	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, End of Cycle 1 (21 days)
Primary	Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRa) and PGDFR Beta (ß) in Tumor Tissue	Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRa.	Baseline, End of Cycle 1 (21 days)
Primary	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 a and ß.	Baseline, End of Cycle 1 (21 days)
Secondary	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.	Baseline to Objective Progression or Death from Any Cause (Up to 18 Months)
Secondary	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.	Baseline to Measured Progressive Disease (Up to 18 Months)
Secondary	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.	Baseline to Measured Progressive Disease (Up to 18 Months)
Secondary	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.	Cycle 1 through Cycle 7 (Up to 6 Months)
Secondary	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy	Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8	Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion
Secondary	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab	Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.	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
Secondary	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.	Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months)

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