Clinical trial NCT01185964: A Study of Olaratumab in Soft Tissue Sarcoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Sarcoma, Soft Tissue
Keywords: Sarcoma, Soft Tissue
Advanced Soft Tissue Sarcoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-08-20
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months)
measure: 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
timeFrame: Baseline Up to 30 Months
Secondary outcomes:
measure: Number of Participants With AEs and SAEs for Phase 2 Portion
timeFrame: Baseline, Up to 30 Months
measure: Overall Survival (OS)
timeFrame: Randomization to the Date of Death From Any Cause (Up To 47 Months)
measure: Percentage of Participants With Objective Response (Objective Response Rate)
timeFrame: Randomization Until Progressive Disease (Up to 30 Months)
measure: Percentage of Participants Who Are Progression-Free (PFS) at 3 Months
timeFrame: Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months)
measure: Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab
timeFrame: 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
measure: PK: Minimum Concentration (Cmin) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
timeFrame: Cycle 1 Day 8: Preinfusion, 1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr, 24hr,72hr,168hr Post Infusion
measure: PK: Area Under Concentration Curve Versus Time (AUCτ) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
timeFrame: Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion
measure: PK: Half-Life (T1/2) Cycle 1 Day 8, Cycle 3 Day 8 of Olaratumab
timeFrame: Cycle 1 Day 8:Preinfusion,1hr,72hr,168hr Post Infusion; Cycle 3 Day 8: Preinfusion,1hr,24hr,72hr,168hr Post Infusion
measure: Percentage of Participants With Anti-Olaratumab Antibody Assessment
timeFrame: Baseline, Up to 30 Months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: ImClone Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: ImClone Investigational Site
state: California
city: Aurora
country: United States
facility: ImClone Investigational Site
state: Colorado
city: Gainesville
country: United States
facility: ImClone Investigational Site
state: Florida
city: Orlando
country: United States
facility: ImClone Investigational Site
state: Florida
city: Atlanta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Chicago
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Rochester
country: United States
facility: ImClone Investigational Site
state: Minnesota
city: St Louis
country: United States
facility: ImClone Investigational Site
state: Missouri
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
city: Charlotte
country: United States
facility: ImClone Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Charleston
country: United States
facility: ImClone Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: ImClone Investigational Site
state: Texas
city: Seattle
country: United States
facility: ImClone Investigational Site
state: Washington
city: Madison
country: United States
facility: ImClone Investigational Site
state: Wisconsin
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.