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

Tracking Information

• First Submitted Date: August 19, 2010
• First Posted Date: August 20, 2010
• Results First Submitted Date: November 18, 2016
• Results First Posted Date: April 14, 2017
• Last Update Posted Date: April 14, 2017
• Study Start Date: October 2010
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 3, 2017)

• 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.

Original Primary Outcome Measures (submitted: August 19, 2010)

• Progression-free survival (PFS) [ Time Frame: 23 months ]
  PFS is the primary outcome for the Phase 2 portion of the study. PFS is measured from the date of randomization until the first radiographic documentation of objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause.
• Summary of Safety for the Phase 1b Portion of the Study [ Time Frame: up to 24 weeks ]

Current Secondary Outcome Measures (submitted: March 3, 2017)

• 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.

Original Secondary Outcome Measures (submitted: August 19, 2010)

• Overall Survival (OS) [ Time Frame: 23 months ]
  Date of randomization to the date of death from any cause
• Percentage of Participants with Objective Response (Objective Response Rate) [ Time Frame: 23 months ]
  Percentage of participants achieving a best overall response of partial or complete response (PR + CR), according to RECIST from the start of treatment until disease progression or occurrence.
• Pharmacokinetic (PK) Profile of IMC-3G3 [ Time Frame: up to week 24 ]
• Proportion of Participants Who are Progression-free (PFS) at 3 Months [ Time Frame: 3 months ]
  The 3 month progression-free survival (PFS) rate is defined as the proportion of participants that are alive and progression-free 3 months after randomization. PFS is measured from the date of randomization until the first radiographic documentation of objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) or death from any cause.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Sarcoma, Soft Tissue

Intervention

• 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.

Study Arms

• 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

  Interventions:

  • Biological: Olaratumab
  • Drug: doxorubicin
• 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

  Interventions:

  • Biological: Olaratumab
  • Drug: doxorubicin
• 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.

  Intervention: Drug: doxorubicin

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 3, 2017): 148
• Original Estimated Enrollment (submitted: August 19, 2010): 130
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01185964
• Other Study ID Numbers: 14055; I5B-IE-JGDG ( Other Identifier: Eli Lilly and Company ); CP15-0806 ( Other Identifier: ImClone Systems )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Chief Medical Officer, ImClone LLC
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: March 2017