A Study of Olaratumab in Soft Tissue Sarcoma

NCT01185964 | Completed Phase 1 Results

• 3 other identifiers: 14055I5B-IE-JGDGCP15-0806
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 17

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.

Conditions

Sarcoma, Soft Tissue

Keywords

Sarcoma, Soft Tissue; Advanced Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS)

  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.

  Randomization Until the First Radiographic Documentation of Objective Progression (Up to 29 Months)

• 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

  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.

  Baseline Up to 30 Months

Secondary Outcomes (9)

• Number of Participants With AEs and SAEs for Phase 2 Portion

  Baseline, Up to 30 Months

• Overall Survival (OS)

  Randomization to the Date of Death From Any Cause (Up To 47 Months)

• Percentage of Participants With Objective Response (Objective Response Rate)

  Randomization Until Progressive Disease (Up to 30 Months)

• Percentage of Participants Who Are Progression-Free (PFS) at 3 Months

  Randomization Until First Radiographic PD or Death from Any Cause (Up to 3 Months)

• Pharmacokinetic (PK) Maximum Concentration (Cmax) Cycle 1 Day 1, Cycle 3 Day 1 of Olaratumab

  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

Study Arms (3)

Phase 1b: Olaratumab + doxorubicin

EXPERIMENTAL

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; Drug: doxorubicin

Phase 2: Olaratumab and doxorubicin

EXPERIMENTAL

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; Drug: doxorubicin

Phase 2: Doxorubicin: Optional Olaratumab After Progression

ACTIVE COMPARATOR

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

Interventions

Olaratumab BIOLOGICAL

Olaratumab 15 mg/kg by intravenous transfusion (I.V.) on days 1+8 of a 21-day cycle

Also known as: LY3012207, IMC-3G3

Phase 1b: Olaratumab + doxorubicin; Phase 2: Olaratumab and doxorubicin

doxorubicin DRUG

Doxorubicin 75 mg/m2 by intravenous injection on day 1 of the 21-day cycle.

Phase 1b: Olaratumab + doxorubicin; Phase 2: Doxorubicin: Optional Olaratumab After Progression; Phase 2: Olaratumab and doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (17)

ImClone Investigational Site

Tucson, Arizona, 85724, United States

Location

ImClone Investigational Site

Los Angeles, California, 90024, United States

Location

ImClone Investigational Site

Aurora, Colorado, 80045, United States

Location

ImClone Investigational Site

Gainesville, Florida, 32608, United States

Location

ImClone Investigational Site

Orlando, Florida, 32806, United States

Location

ImClone Investigational Site

Atlanta, Georgia, 30308, United States

Location

ImClone Investigational Site

Chicago, Illinois, 60611, United States

Location

ImClone Investigational Site

Rochester, Minnesota, 55902, United States

Location

ImClone Investigational Site

St Louis, Missouri, 63110, United States

Location

ImClone Investigational Site

New York, New York, 10065, United States

Location

ImClone Investigational Site

Charlotte, North Carolina, 28203, United States

Location

ImClone Investigational Site

Cleveland, Ohio, 44106, United States

Location

ImClone Investigational Site

Charleston, South Carolina, 29425, United States

Location

ImClone Investigational Site

Memphis, Tennessee, 38119, United States

Location

ImClone Investigational Site

San Antonio, Texas, 78229, United States

Location

ImClone Investigational Site

Seattle, Washington, 98109, United States

Location

ImClone Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 27291997 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

olaratumab; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2010
• First Posted: August 20, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: April 1, 2016
• Last Updated: April 14, 2017
• Results First Posted: April 14, 2017

Record last verified: 2017-03

Locations

US (17)