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

• ClinicalTrials.gov Identifier: NCT02326025
• Recruitment Status: Completed
• First Posted: December 25, 2014
• Results First Posted: November 21, 2019
• Last Update Posted: November 21, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

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.

Condition or disease	Intervention/treatment	Phase
Sarcoma, Soft Tissue	Drug: Olaratumab; Drug: Doxorubicin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 49 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: January 22, 2015
• Actual Primary Completion Date: May 20, 2015
• Actual Study Completion Date: November 2, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A; 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.	Drug: Olaratumab; Administered IV; Other Names: LY3012207; IMC-3G3; Drug: Doxorubicin; Administered IV
Experimental: Part B; 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.	Drug: Olaratumab; Administered IV; Other Names: LY3012207; IMC-3G3; Drug: Doxorubicin; Administered IV

Outcome Measures

Primary Outcome Measures :

1. 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 ]
2. 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 Measures :

1. 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 ]
2. PK: AUC Zero to Time t, Where t is the Last Time Point (0-tLast) Olaratumab [ 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 ]
   PK: AUC (0-tLast) with a measurable concentration. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
3. PK: Cmax Olaratumab [ 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 ]
   PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
4. PK: Tmax Olaratumab [ 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 ]
   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.
5. Percentage of Participants With Olaratumab Antibodies [ 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 ]
   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.
6. Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [ Time Frame: Baseline to Measured Progressive Disease, Study Discontinuation or Death (Up to 24 Months) ]
   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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

UCLA Medical Center

Los Angeles, California, United States, 90095

United States, Colorado

University of Colorado Cancer Center

Aurora, Colorado, United States, 80045

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Indiana

IU Simon Cancer Center

Indianapolis, Indiana, United States, 46202

United States, Missouri

Washington University Medical Center

Saint Louis, Missouri, United States, 63110

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• 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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02326025
• Other Study ID Numbers: 15676; I5B-EW-JGDI ( Other Identifier: Eli Lilly and Company )
• First Posted: December 25, 2014
• Results First Posted: November 21, 2019
• Last Update Posted: November 21, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

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