A Study of Olaratumab and Doxorubicin in Participants With Advanced Soft Tissue Sarcoma
- Registration Number
- NCT02326025
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A Olaratumab 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. Part A Doxorubicin 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. Part B Olaratumab 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. Part B Doxorubicin 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.
- Primary Outcome Measures
Name Time Method Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin Cycle(C)1 and (C)2, Day(D)1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hours (Hrs) Post dose PK: Maximum Concentration (Cmax) Doxorubicin C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose
- Secondary Outcome Measures
Name Time Method PK:Time of Maximum Observed Concentration (Tmax) Doxorubicin C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose PK: AUC Zero to Time t, Where t is the Last Time Point (0-tLast) Olaratumab 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.
PK: Cmax Olaratumab 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.
PK: Tmax Olaratumab 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.
Percentage of Participants With Olaratumab Antibodies 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.
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] 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.
Trial Locations
- Locations (6)
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Washington University Medical Center
🇺🇸Saint Louis, Missouri, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
IU Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States