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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02783599
Recruitment Status : Completed
First Posted : May 26, 2016
Results First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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).

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Drug: Olaratumab Drug: Doxorubicin Radiation: External Beam Radiotherapy Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 11, 2016
Actual Primary Completion Date : July 5, 2018
Actual Study Completion Date : July 5, 2018


Arm Intervention/treatment
Experimental: Olaratumab + Doxorubicin

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).

Drug: Olaratumab
Administered IV
Other Name: LY3012207

Drug: Doxorubicin
Administered IV

Experimental: Olaratumab + Radiotherapy Addendum

Olaratumab given IV on Day 1 and Day 8 (21 day cycle) concurrently with radiotherapy.

Radiotherapy addendum was not implemented.

Drug: Olaratumab
Administered IV
Other Name: LY3012207

Radiation: External Beam Radiotherapy



Primary Outcome Measures :
  1. Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood [ Time Frame: Baseline, End of Cycle 1 (21 days) ]
    Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.

  2. Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue [ Time Frame: Baseline, End of Cycle 1 (21 days) ]
    Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.

  3. Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue [ Time Frame: Baseline, End of Cycle 1 (21 days) ]
    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 :
  1. Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death from Any Cause (Up to 18 Months) ]
    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.

  2. Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Measured Progressive Disease (Up to 18 Months) ]
    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.

  3. Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR [ Time Frame: Baseline to Measured Progressive Disease (Up to 18 Months) ]

    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.


  4. Percentage of Participants With Resectable Tumors (Resectability Rate) [ Time Frame: Cycle 1 through Cycle 7 (Up to 6 Months) ]
    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.

  5. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy [ Time Frame: Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion ]
    Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8

  6. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab [ 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 ]
    Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.

  7. Number of Participants With Anti-Olaratumab Antibodies [ Time Frame: Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months) ]
    A participant is counted as positive if they had at least one anti-olaratumab antibody positive result during the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02783599


Locations
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United States, California
USC/Norris Comp Cancer Center
Los Angeles, California, United States, 90033
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Florida
All Children's Hospital
Saint Petersburg, Florida, United States, 33701
Moffitt Cancer Center & Research Inst
Tampa, Florida, United States, 33612
United States, Kansas
Kansas City Cancer Center
Overland Park, Kansas, United States, 66210
United States, Missouri
Washington University Medical Center
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Levine Children's Hospital
Charlotte, North Carolina, United States, 28203
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Mary Crowley Cancer Research
Dallas, Texas, United States, 75230
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, France, 69373
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, Italy, 20133
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, 08025
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, Spain, 41013
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 Kingdom, SW3 6JJ
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] May 8, 2017
Statistical Analysis Plan  [PDF] July 20, 2017


Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02783599    
Other Study ID Numbers: 15840
I5B-MC-JGDM ( Other Identifier: Eli Lilly and Company )
2015-005018-31 ( EudraCT Number )
First Posted: May 26, 2016    Key Record Dates
Results First Posted: August 12, 2019
Last Update Posted: August 12, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Olaratumab
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action