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Trial record 1 of 1 for:    NCT01185964
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A Study of Olaratumab in Soft Tissue Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01185964
First received: August 19, 2010
Last updated: March 3, 2017
Last verified: March 2017
  Purpose
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 Intervention Phase
Sarcoma, Soft Tissue Biological: Olaratumab Drug: doxorubicin Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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.

  • 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:
  • 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.

  • 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.

  • 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%.

  • 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.

  • 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 ]
  • 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 ]
  • 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.

  • 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 ]
  • 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.


Enrollment: 148
Study Start Date: October 2010
Study Completion Date: April 2016
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185964

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):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01185964     History of Changes
Other Study ID Numbers: 14055
I5B-IE-JGDG ( Other Identifier: Eli Lilly and Company )
CP15-0806 ( Other Identifier: ImClone Systems )
Study First Received: August 19, 2010
Results First Received: November 18, 2016
Last Updated: March 3, 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
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 27, 2017