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A Study of Olaratumab and Doxorubicin in Participants With Advanced 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 basic science trial for Sarcoma, Soft Tissue

Eligibility Criteria

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

Inclusion Criteria:

  • Have histological or cytological evidence of a diagnosis of soft tissue sarcoma (STS) that is advanced and/or metastatic
  • Have the presence of measurable and/or nonmeasurable disease
  • Have given written informed consent prior to any study-specific procedures
  • Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Have discontinued previous treatments for cancer and recovered from the acute effects of therapy
  • Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

  • Have received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device for noncancer indications
  • Have received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
  • Have active central nervous system (CNS) metastasis. Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids
  • Have unstable hepatic disease with a grade equal to or greater than Child-Pugh B
  • Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis
  • Have a history of another primary cancer, with the exception of a) curatively resected nonmelanoma 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
  • Have a history of chronic heart failure or left ventricular dysfunction
  • Have a resting heart rate of less than (<)50 beats per minute (bpm) or greater than (>)100 bpm
  • Have a history of radiation therapy involving the mediastinal/pericardial area. Previous radiation therapy is allowed but must not have included whole pelvis radiation

Sites / Locations

  • UCLA Medical Center
  • University of Colorado Cancer Center
  • Northwestern University
  • IU Simon Cancer Center
  • Washington University Medical Center
  • Seattle Cancer Care Alliance

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part A

Part B

Arm Description

Doxorubicin Alone: On Cycle 1, Day 1, participants received 75 milligram/square meter (mg/m2) of doxorubicin intravenously (IV). Olaratumab Alone: On Cycle 1, Day 10, participants received 15 milligram/kilogram (mg/kg) of olaratumab IV. Olaratumab + Doxorubicin: For Cycles 2 to 8, participants received 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, IV and 75 mg/m2 of doxorubicin IV immediately following the completion of the olaratumab infusion. Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onward, until discontinuation criteria are met.

Doxorubicin Alone: On Cycle 1, Day 1, participants received doxorubicin 75 mg/m2 IV Olaratumab Alone: On Cycle 1, Day 10, participants received 20 mg/kg of olaratumab IV. Olaratumab + Doxorubicin: For Cycle 2, participants received 20 mg of olaratumab on Days 1 and 8 of each 21-day cycle, IV. On Day 1 of Cycle 2, doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion. For Cycles 3 - 8, Day 1 and 8, olaratumab 15 mg/kg was administered and on Day 1 doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion. Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onwards, until discontinuation criteria are met.

Outcomes

Primary Outcome Measures

Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin
PK: Maximum Concentration (Cmax) Doxorubicin

Secondary Outcome Measures

PK:Time of Maximum Observed Concentration (Tmax) Doxorubicin
PK: AUC Zero to Time t, Where t is the Last Time Point (0-tLast) Olaratumab
PK: AUC (0-tLast) with a measurable concentration. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
PK: Cmax Olaratumab
PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
PK: Tmax Olaratumab
Tmax times are relative to the start of the approximately 60-minute IV infusion of olaratumab. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
Percentage of Participants With Olaratumab Antibodies
The formation of anti-drug antibodies (ADA) was assessed using validated ELISAs, following a 4-tier approach. Both the ADA screening assay and the neutralizing antibody assay were validated in accordance with the US Food and Drug Administration (FDA) Guidance for Industry. Participants who had positive samples for treatment emergence due to being <4-fold difference from baseline or occurred prior to drug exposure are reported.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
The percentage of participants with a best overall response achieving CR or PR (ORR) was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. The methodology for the confidence interval calculation is the "exact F" method.

Full Information

First Posted
December 22, 2014
Last Updated
October 31, 2019
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT02326025
Brief Title
A Study of Olaratumab and Doxorubicin in Participants With Advanced Soft Tissue Sarcoma
Official Title
An Open-Label Study to Evaluate the Pharmacokinetics of Doxorubicin Following the Concomitant Intravenous Administration of Olaratumab (IMC-3G3) to Patients With Advanced Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
January 22, 2015 (Actual)
Primary Completion Date
May 20, 2015 (Actual)
Study Completion Date
November 2, 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 assess how the body handles olaratumab when it is given with another drug called doxorubicin. The safety and tolerability of these drugs will be studied. Each participant will complete two 21-day cycles in a fixed order. Participants who complete Cycle 2 may continue to receive olaratumab + doxorubicin for an additional six 21-day cycles and then may receive olaratumab alone until discontinuation criteria are met. Screening is required within 21 days prior to first dose. Part B was added in October, 2015 to assess how the body handles a higher dose of olaratumab when given with doxorubicin. Participants may only enroll in one part.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part A
Arm Type
Experimental
Arm Description
Doxorubicin Alone: On Cycle 1, Day 1, participants received 75 milligram/square meter (mg/m2) of doxorubicin intravenously (IV). Olaratumab Alone: On Cycle 1, Day 10, participants received 15 milligram/kilogram (mg/kg) of olaratumab IV. Olaratumab + Doxorubicin: For Cycles 2 to 8, participants received 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, IV and 75 mg/m2 of doxorubicin IV immediately following the completion of the olaratumab infusion. Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onward, until discontinuation criteria are met.
Arm Title
Part B
Arm Type
Experimental
Arm Description
Doxorubicin Alone: On Cycle 1, Day 1, participants received doxorubicin 75 mg/m2 IV Olaratumab Alone: On Cycle 1, Day 10, participants received 20 mg/kg of olaratumab IV. Olaratumab + Doxorubicin: For Cycle 2, participants received 20 mg of olaratumab on Days 1 and 8 of each 21-day cycle, IV. On Day 1 of Cycle 2, doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion. For Cycles 3 - 8, Day 1 and 8, olaratumab 15 mg/kg was administered and on Day 1 doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion. Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onwards, until discontinuation criteria are met.
Intervention Type
Drug
Intervention Name(s)
Olaratumab
Other Intervention Name(s)
LY3012207, IMC-3G3
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin
Time Frame
Cycle(C)1 and (C)2, Day(D)1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hours (Hrs) Post dose
Title
PK: Maximum Concentration (Cmax) Doxorubicin
Time Frame
C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose
Secondary Outcome Measure Information:
Title
PK:Time of Maximum Observed Concentration (Tmax) Doxorubicin
Time Frame
C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose
Title
PK: AUC Zero to Time t, Where t is the Last Time Point (0-tLast) Olaratumab
Description
PK: AUC (0-tLast) with a measurable concentration. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
Time Frame
C1 D10: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose
Title
PK: Cmax Olaratumab
Description
PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
Time Frame
C1 D10:Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose
Title
PK: Tmax Olaratumab
Description
Tmax times are relative to the start of the approximately 60-minute IV infusion of olaratumab. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
Time Frame
C1 D10: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose
Title
Percentage of Participants With Olaratumab Antibodies
Description
The formation of anti-drug antibodies (ADA) was assessed using validated ELISAs, following a 4-tier approach. Both the ADA screening assay and the neutralizing antibody assay were validated in accordance with the US Food and Drug Administration (FDA) Guidance for Industry. Participants who had positive samples for treatment emergence due to being <4-fold difference from baseline or occurred prior to drug exposure are reported.
Time Frame
Preinfusion on Day 1 of Cycles 1 through 3 and Preinfusion on Day 1 of Every Second Cycle Thereafter, Up to 30-Day Follow Up
Title
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Description
The percentage of participants with a best overall response achieving CR or PR (ORR) was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. The methodology for the confidence interval calculation is the "exact F" method.
Time Frame
Baseline to Measured Progressive Disease, Study Discontinuation or Death (Up to 24 Months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Have histological or cytological evidence of a diagnosis of soft tissue sarcoma (STS) that is advanced and/or metastatic Have the presence of measurable and/or nonmeasurable disease Have given written informed consent prior to any study-specific procedures Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale Have discontinued previous treatments for cancer and recovered from the acute effects of therapy Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures Exclusion Criteria: Have received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device for noncancer indications Have received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones Have active central nervous system (CNS) metastasis. Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids Have unstable hepatic disease with a grade equal to or greater than Child-Pugh B Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis Have a history of another primary cancer, with the exception of a) curatively resected nonmelanoma 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 Have a history of chronic heart failure or left ventricular dysfunction Have a resting heart rate of less than (<)50 beats per minute (bpm) or greater than (>)100 bpm Have a history of radiation therapy involving the mediastinal/pericardial area. Previous radiation therapy is allowed but must not have included whole pelvis radiation
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
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
IU Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Washington University Medical Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study of Olaratumab and Doxorubicin in Participants With Advanced Soft Tissue Sarcoma

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