A Study of Olaratumab in Soft Tissue Sarcoma

• ClinicalTrials.gov Identifier: NCT01185964
• Recruitment Status: Completed
• First Posted: August 20, 2010
• Results First Posted: April 14, 2017
• Last Update Posted: April 14, 2017
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The main purpose of this study is to gather information about the use of an investigational drug called olaratumab with a drug for soft tissue sarcoma called doxorubicin.

Condition or disease	Intervention/treatment	Phase
Sarcoma, Soft Tissue	Biological: Olaratumab; Drug: doxorubicin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b/2, With Phase 2 Randomized, Study Evaluating the Efficacy of Doxorubicin With or Without a Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) in the Treatment of Advanced Soft Tissue Sarcoma
• Study Start Date: October 2010
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1b: Olaratumab + doxorubicin; All cycles are 21 days. Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1 All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8	Biological: Olaratumab; Olaratumab 15 mg/kg by intravenous transfusion (I.V.) on days 1+8 of a 21-day cycle; Other Names: LY3012207; IMC-3G3; Drug: doxorubicin; Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.
Experimental: Phase 2: Olaratumab and doxorubicin; All cycles are 21 days. Cycles 1-8: Olaratumab 15 mg/kg on days 1+8, and doxorubicin 75 mg/m2 on day 1 All subsequent cycles until progression: Olaratumab 15 mg/kg on days 1+8	Biological: Olaratumab; Olaratumab 15 mg/kg by intravenous transfusion (I.V.) on days 1+8 of a 21-day cycle; Other Names: LY3012207; IMC-3G3; Drug: doxorubicin; Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.
Active Comparator: Phase 2: Doxorubicin: Optional Olaratumab After Progression; All cycles are 21 days. Cycles 1-8: doxorubicin 75 mg/m2 on day 1 until disease progression. At disease progression: optional Olaratumab 15 mg/kg on days 1+8 until further progression.	Drug: doxorubicin; Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months) ]
   PFS is measured from randomization until the first radiographic documentation of progression of disease (PD) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause. Participants who died without PD was considered to have progressed on the day of death. The following censoring rules applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization. Participants were censored at the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last adequate radiographic visit. If participant started new treatment before PD, the participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
2. Number of Participants With Treatment Related Adverse Events (TEAE), Adverse Events (AE) or Serious Adverse Events (SAE) for Safety for the Phase 1b Portion of the Study [ Time Frame: Baseline Up to 30 Months ]
   All Phase 1b participants who experienced at least 1 TEAE in the Phase 1b portion of the study. Adverse Event with missing relationship to study is counted as related. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.

Secondary Outcome Measures :

1. Number of Participants With AEs and SAEs for Phase 2 Portion [ Time Frame: Baseline, Up to 30 Months ]
   A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
2. Overall Survival (OS) [ Time Frame: Randomization to the Date of Death From Any Cause (Up To 47 Months) ]
   OS was defined as the date of randomization to the date of death from any cause. Reasons for censoring OS were that participant was known to be alive, participant was lost to follow up during the study or participant withdrew consent to follow up.
3. Percentage of Participants With Objective Response (Objective Response Rate) [ Time Frame: Randomization Until Progressive Disease (Up to 30 Months) ]
   Objective Response Rate (ORR) is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%.
4. Percentage of Participants Who Are Progression-Free (PFS) at 3 Months [ Time Frame: Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months) ]
   (PFS) rate is defined as the percentage of participants that are alive and progression-free 3 months after randomization. PFS is measured from randomization until the first radiographic progressive disease as defined by RECIST (version 1.1) or death from any cause. Participants who died without PD were considered to have progressed on the day of death. Censoring applied: If no radiologic assessment at baseline or post baseline, participant was censored at the date of randomization or the day of their last tumor assessment if no PD and were lost to follow up; If death or PD occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit. If participant started new treatment before PD, participant was censored at the date of last tumor assessment prior to new therapy. If treatment was discontinued for reasons other than PD and no further assessment, censoring occurred at last tumor assessment.
5. Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab [ Time Frame: Cycle 1 Day 1: Preinfusion, End of Infusion,1hr,48hr,72hr,168 hr Post infusion; Cycle 3 Day 1:Preinfusion, End of Infusion,1hr,24hr,48hr,72hr,168hr Post Infusion ]
6. PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab [ Time Frame: Cycle 1 Day 8: Preinfusion, 1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr, 24hr,72hr,168hr Post Infusion ]
7. PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab [ Time Frame: Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion ]
   AUCτ = area under the concentration versus time curve during one dosing interval with a measurable concentration.
8. PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab [ Time Frame: Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion ]
9. Percentage of Participants With Anti-Olaratumab Antibody Assessment [ Time Frame: Baseline, Up to 30 Months ]
   Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

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:

• The participant has histologically- or cytologically-confirmed malignant soft tissue sarcoma
• The participant has advanced soft tissue sarcoma (STS), not amenable to treatment with surgery or radiotherapy
• The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0-2
• The participant has available tumor tissue from either the primary or metastatic tumor for determination of PDGFRα expression
• The participant has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥ 1500 μL, hemoglobin ≥ 9.0 g/dL, and a platelet count of 100,000/μL obtained within 2 weeks prior to study entry
• The participant has adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN)
• The participant has adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN. If creatinine is above the ULN, the participant's creatinine clearance is ≥ 45 mL/min
• Because the teratogenicity of Olaratumab is not known, women of childbearing potential (WOCBP) and sexually active males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation

Exclusion Criteria:

• The participant has histologically- or cytologically-confirmed Kaposi's sarcoma
• The participant has untreated central nervous system metastases
• The participant received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones (ie, mitoxantrone)
• The participant received prior radiation therapy to the mediastinal/pericardial area
• The participant has a history of another primary cancer, with the exception of a) curatively resected nonmelanomatous 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
• The participant is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy, or an investigational agent
• The participant has an elective or a planned major surgery to be performed during the course of the study
• The participant has an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, requiring parenteral antibiotics, symptomatic congestive heart failure, severe myocardial insufficiency, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction 6 months prior to study entry
• The participant has known immunodeficiency virus (HIV) infection
• The participant, if female, is pregnant or lactating
• The participant has a known allergy to any of the treatment components

Contacts and Locations

Locations

United States, Arizona

ImClone Investigational Site

Tucson, Arizona, United States, 85724

United States, California

ImClone Investigational Site

Los Angeles, California, United States, 90024

United States, Colorado

ImClone Investigational Site

Aurora, Colorado, United States, 80045

United States, Florida

ImClone Investigational Site

Gainesville, Florida, United States, 32608

ImClone Investigational Site

Orlando, Florida, United States, 32806

United States, Georgia

ImClone Investigational Site

Atlanta, Georgia, United States, 30308

United States, Illinois

ImClone Investigational Site

Chicago, Illinois, United States, 60611

United States, Minnesota

ImClone Investigational Site

Rochester, Minnesota, United States, 55902

United States, Missouri

ImClone Investigational Site

St Louis, Missouri, United States, 63110

United States, New York

ImClone Investigational Site

New York, New York, United States, 10065

United States, North Carolina

ImClone Investigational Site

Charlotte, North Carolina, United States, 28203

United States, Ohio

ImClone Investigational Site

Cleveland, Ohio, United States, 44106

United States, South Carolina

ImClone Investigational Site

Charleston, South Carolina, United States, 29425

United States, Tennessee

ImClone Investigational Site

Memphis, Tennessee, United States, 38119

United States, Texas

ImClone Investigational Site

San Antonio, Texas, United States, 78229

United States, Washington

ImClone Investigational Site

Seattle, Washington, United States, 98109

United States, Wisconsin

ImClone Investigational Site

Madison, Wisconsin, United States, 53792

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. doi: 10.1016/S0140-6736(16)30587-6. Epub 2016 Jun 9. Erratum In: Lancet. 2016 Jul 30;388(10043):464.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01185964
• Other Study ID Numbers: 14055; I5B-IE-JGDG ( Other Identifier: Eli Lilly and Company ); CP15-0806 ( Other Identifier: ImClone Systems )
• First Posted: August 20, 2010
• Results First Posted: April 14, 2017
• Last Update Posted: April 14, 2017
• Last Verified: March 2017

Keywords provided by Eli Lilly and Company:

Sarcoma, Soft Tissue; Advanced Soft Tissue Sarcoma

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