Clinical trial NCT02783599: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Soft Tissue Sarcoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-05-26
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood
timeFrame: Baseline, End of Cycle 1 (21 days)
measure: Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue
timeFrame: Baseline, End of Cycle 1 (21 days)
measure: Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue
timeFrame: Baseline, End of Cycle 1 (21 days)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Progression or Death from Any Cause (Up to 18 Months)
measure: Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline to Measured Progressive Disease (Up to 18 Months)
measure: Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR
timeFrame: Baseline to Measured Progressive Disease (Up to 18 Months)
measure: Percentage of Participants With Resectable Tumors (Resectability Rate)
timeFrame: Cycle 1 through Cycle 7 (Up to 6 Months)
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy
timeFrame: Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab
timeFrame: 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
measure: Number of Participants With Anti-Olaratumab Antibodies
timeFrame: Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comp Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center & Research Inst
state: Florida
city: Overland Park
country: United States
facility: Kansas City Cancer Center
state: Kansas
city: Saint Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Lyon
country: France
facility: 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
country: Italy
facility: 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
country: Spain
facility: 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
country: Spain
facility: 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
country: United Kingdom
facility: 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.
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: