A Study of Olaratumab in Japanese Participants With Advanced Cancer

Study Overview
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Brief Summary
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This study consists of 2 parts (Part A and Part B). The main purpose of Part A is to evaluate safety and side effects of olaratumab in combination with doxorubicin in Japanese participants with a group of rare cancers (advanced solid tumors, especially advanced soft tissue sarcoma [STS].) The main purpose of Part B is to evaluate how much olaratumab gets into the blood stream of Japanese participants with advanced solid tumors and how long it takes the body to get rid of it.

Official Title
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A Phase 1 Study of Olaratumab in Japanese Patients With Advanced Soft Tissue Sarcoma or Advanced Solid Tumors

Conditions
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Neoplasm

Intervention / Treatment
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* Biological: Olaratumab
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A: Have histological or cytological evidence of a diagnosis of advanced or metastatic solid tumor, especially STS, which is not amenable to treatment with surgery or radiotherapy. Part B: Have histological or cytological evidence of a diagnosis of solid tumor that is advanced or metastatic. Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Have given written informed consent prior to any study-specific procedures. Have adequate organ and coagulation function Have an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of less than or equal to 1. Have discontinued previous treatments for cancer and recovered from the acute effects of therapy. (Part A only) Have a prestudy echocardiogram with an actual left ventricular ejection fraction greater than or equal to 50%, within 21 days prior to first dose of study medication. All participants agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following last dose of study drug. Female participants: must either be women not of child-bearing potential due to surgical sterilization confirmed by medical history, or menopause or women of child-bearing potential who test negative for pregnancy within 7 days before the first dose of study drug based on serum or urine pregnancy test and agree not to breast feed during the study and for 3 months following the last dose of the study drug(s) Have an estimated life expectancy of more than or equal to 3 months in the judgment of the investigator. Exclusion Criteria: Have received treatment within 21 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device for non-cancer indications or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. (Part A only) Have received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (Part A only) Have received prior radiation therapy to the mediastinal/pericardial area. Have symptomatic central nervous system malignancy or metastasis. Participants with treated central nervous system (CNS) metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 60 days. Have an elective or a planned major surgery to be performed during the course of the study. Have an uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure greater than class II of the New York Heart Association guideline, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Have unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry. Have a known allergy to any of the treatment components. Have a history of allergic reactions attributed to compounds of chemical or biologic composition similar to that of olaratumab. Have a known active fungal, bacterial, and/or known viral infection Have a corrected QT interval of greater than 470 milliseconds (msec) on screening electrocardiogram (ECG) Have a second primary malignancy that, in the judgment of the investigator and sponsor, may affect the interpretation of results.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A cohort 1: Olaratumab+Doxorubicin<br>15 milligram per kilogram (mg/kg) of olaratumab administered intravenously (IV) on Day 1 and Day 8, and 25 milligram per square meter (mg/m2) of doxorubicin administered IV on Day 1, Day 2, and Day 3 every 21-day cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met . | Biological: Olaratumab<br>* Administered IV<br>* Other names: IMC-3G3;Drug: Doxorubicin<br>* Administered IV<br>|
| Experimental: Part A cohort 2: Olaratumab+Doxorubicin<br>15 mg/kg of olaratumab administered IV on Day 1 and Day 8, and 75 mg/m2 of doxorubicin administered IV on Day 1 every 21 day-cycle for up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met. | Biological: Olaratumab<br>* Administered IV<br>* Other names: IMC-3G3;Drug: Doxorubicin<br>* Administered IV<br>|
| Experimental: Part A cohort 3 Olaratumab + Doxorubicin<br>20 mg/kg loading dose of olaratumab administered IV on Day 1 and Day 8 in Cycle 1, followed by 15 mg/kg IV on Day 1 and Day 8 in subsequent cycles, and 75 mg/m2 of doxorubicin administered IV on Day 1 of every 21 day-cycle up to 6 cycles or until the cumulative dose of doxorubicin reached 500 mg/m2, whichever came later, followed by 15 mg/kg of olaratumab IV monotherapy on Day 1 and Day 8 in subsequent cycles. Participants may continue to receive treatment until discontinuation criteria are met. | Biological: Olaratumab<br>* Administered IV<br>* Other names: IMC-3G3;Drug: Doxorubicin<br>* Administered IV<br>|
| Experimental: Part B: Olaratumab<br>15 mg/kg olaratumab administered IV on Day 1 and Day 8 of every 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | Biological: Olaratumab<br>* Administered IV<br>* Other names: IMC-3G3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. | Baseline to Study completion (Up To 3.5 Years) | 
| Part A: Number of Participants With Dose Limiting Toxicities (DLTs) | DLT is defined as adverse event (AE) during Cycle 1 (Days 1 through 21) that was possibly related to the study drug and toxicities considered by the investigator as dose limiting. A summary of other nonserious AEs, and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section. | Cycle 1 (21 Days) | 
| Part B: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Maximum observed serum concentration (Cmax) of olaratumab is reported. | Cycle (C) 1 Day (D) 1 and C3 D1: Pre-infusion, Immediately postinfusion and 1, 24, 48, 72 and 168 hours (h) postinfusion; C1 D8 and C3 D8: Pre- infusion, Immediately postinfusion and 1, 48, 72, 168 and 336 h postinfusion | 
| Part B: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | AUC(0-t) hours (h), area under the serum concentration versus time curve from time zero to t hours at AUC(0-168h) for Cycle 1 Day 1 and Cycle 3 Day 1, AUC(0-336h) for Cycle 1 Day 8 and Cycle 3 Day 8 of Olaratumab is reported. | Cycle (C) 1 Day (D) 1 and C3 D1: Pre-infusion, Immediately postinfusion and 1, 24, 48, 72 and 168 hours (h) postinfusion; C1 D8 and C3 D8: Pre- infusion, Immediately postinfusion and 1, 48, 72, 168 and 336 h postinfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Olaratumab | Maximum observed serum concentration (Cmax) of olaratumab is reported. | Cycle (C) 1 Day (D) 1 and C3 D1: Pre-infusion, Immediately postinfusion and 1.5, 24, 48, 72 and 168 hours (h) postinfusion; C1 D8 and C3 D8: Pre- infusion, Immediately postinfusion and 1, 48, 72, 168 and 336 h postinfusion | 
| Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Olaratumab | AUC(0-t) hours (h), area under the serum concentration versus time curve from time zero to t hours at AUC(0-168h) for Cycle 1 Day 1 and Cycle 3 Day 1, AUC(0-336h) for Cycle 1 Day 8 and Cycle 3 Day 8 of Olaratumab is reported. | Cycle (C) 1 Day (D) 1 and C3 D1: Pre-infusion, Immediately postinfusion and 1.5, 24, 48, 72 and 168 hours (h) postinfusion; C1 D8 and C3 D8: Pre- infusion, Immediately postinfusion and 1, 48, 72, 168 and 336 h postinfusion | 
| Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Maximum observed plasma concentration (Cmax) of doxorubicin is reported. | Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 3, Cycle 3 Day 1, Cycle 3 Day 2 and Cycle 3 Day 3: Immediately postinfusion | 
| Part A: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Doxorubicin | Maximum observed plasma concentration (Cmax) of doxorubicin is reported. | Cycle 1 Day 1 and Cycle 3 Day 1: Immediately postinfusion, 0.5, 1, 2, 4, 8, 24, 48, and 72 h postinfusion | 
| Part A: Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of Doxorubicin | Area under the concentration verses time curve from zero to infinity (AUC[0-∞]) of doxorubicin is reported. | Cycle 1 Day 1 and Cycle 3 Day 1: Immediately postinfusion, 0.5, 1, 2, 4, 8, 24, 48, and 72 h postinfusion | 
| Change From Baseline in Percentage of Participants With a Tumor Response | Tumor response was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is greater than or equal to (≥) 30% decrease in sum of longest diameter of target lesions. | Baseline to Study completion (Up To 3.5 Years) |