A Study of Olaratumab and Doxorubicin in Participants With Advanced Soft Tissue Sarcoma

• ClinicalTrials.gov Identifier: NCT02326025
• Recruitment Status: Completed
• First Posted: December 25, 2014
• Results First Posted: November 21, 2019
• Last Update Posted: November 21, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: December 22, 2014
• First Posted Date: December 25, 2014
• Results First Submitted Date: October 31, 2019
• Results First Posted Date: November 21, 2019
• Last Update Posted Date: November 21, 2019
• Actual Study Start Date: January 22, 2015
• Actual Primary Completion Date: May 20, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2019)

• Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin [ Time Frame: Cycle(C)1 and (C)2, Day(D)1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hours (Hrs) Post dose ]
• PK: Maximum Concentration (Cmax) Doxorubicin [ Time Frame: C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose ]

Original Primary Outcome Measures (submitted: December 22, 2014)

• Pharmacokinetics: Area Under The Concentration Curve (AUC) [ Time Frame: Baseline through 10 days after doxorubicin administration in Cycle 1 and through Day 8 of Cycle 2 ]
• Pharmacokinetics: Maximum Concentration (Cmax) [ Time Frame: Baseline through 10 days after doxorubicin administration in Cycle 1 and through Day 8 of Cycle 2 ]

Current Secondary Outcome Measures (submitted: October 31, 2019)

• PK:Time of Maximum Observed Concentration (Tmax) Doxorubicin [ Time Frame: C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose ]
• PK: AUC Zero to Time t, Where t is the Last Time Point (0-tLast) Olaratumab [ Time Frame: C1 D10: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose ]
  PK: AUC (0-tLast) with a measurable concentration. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
• PK: Cmax Olaratumab [ Time Frame: C1 D10:Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose ]
  PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
• PK: Tmax Olaratumab [ Time Frame: C1 D10: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose; C2 D1: Predose, 0, 1, 4, 24, 48, 72, 96 Hrs Post dose ]
  Tmax times are relative to the start of the approximately 60-minute IV infusion of olaratumab. PK data includes Part A Olaratumab alone and Part B Olaratumab + Doxorubicin.
• Percentage of Participants With Olaratumab Antibodies [ Time Frame: Preinfusion on Day 1 of Cycles 1 through 3 and Preinfusion on Day 1 of Every Second Cycle Thereafter, Up to 30-Day Follow Up ]
  The formation of anti-drug antibodies (ADA) was assessed using validated ELISAs, following a 4-tier approach. Both the ADA screening assay and the neutralizing antibody assay were validated in accordance with the US Food and Drug Administration (FDA) Guidance for Industry. Participants who had positive samples for treatment emergence due to being <4-fold difference from baseline or occurred prior to drug exposure are reported.
• Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [ Time Frame: Baseline to Measured Progressive Disease, Study Discontinuation or Death (Up to 24 Months) ]
  The percentage of participants with a best overall response achieving CR or PR (ORR) was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. The methodology for the confidence interval calculation is the "exact F" method.

Original Secondary Outcome Measures (submitted: December 22, 2014)

• Pharmacokinetics: Area Under The Concentration Curve (AUC) [ Time Frame: Post olaratumab dose on Day 10 of Cycle 1 through Day 1 of Cycle 2 ]
• Pharmacokinetics: Maximum Concentration (Cmax) [ Time Frame: Post olaratumab dose in Day 10 of Cycle 1 and through Day 1 of Cycle 2 ]

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

Descriptive Information

• Brief Title: A Study of Olaratumab and Doxorubicin in Participants With Advanced Soft Tissue Sarcoma
• Official Title: An Open-Label Study to Evaluate the Pharmacokinetics of Doxorubicin Following the Concomitant Intravenous Administration of Olaratumab (IMC-3G3) to Patients With Advanced Soft Tissue Sarcoma

Brief Summary

The purpose of this study is to assess how the body handles olaratumab when it is given with another drug called doxorubicin.

The safety and tolerability of these drugs will be studied. Each participant will complete two 21-day cycles in a fixed order. Participants who complete Cycle 2 may continue to receive olaratumab + doxorubicin for an additional six 21-day cycles and then may receive olaratumab alone until discontinuation criteria are met.

Screening is required within 21 days prior to first dose.

Part B was added in October, 2015 to assess how the body handles a higher dose of olaratumab when given with doxorubicin.

Participants may only enroll in one part.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Sarcoma, Soft Tissue

Intervention

• Drug: Olaratumab
  Administered IV
  Other Names:

  • LY3012207
  • IMC-3G3
• Drug: Doxorubicin
  Administered IV

Study Arms

• Experimental: Part A

  Doxorubicin Alone: On Cycle 1, Day 1, participants received 75 milligram/square meter (mg/m2) of doxorubicin intravenously (IV).

  Olaratumab Alone: On Cycle 1, Day 10, participants received 15 milligram/kilogram (mg/kg) of olaratumab IV.

  Olaratumab + Doxorubicin: For Cycles 2 to 8, participants received 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, IV and 75 mg/m2 of doxorubicin IV immediately following the completion of the olaratumab infusion.

  Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onward, until discontinuation criteria are met.

  Interventions:

  • Drug: Olaratumab
  • Drug: Doxorubicin
• Experimental: Part B

  Doxorubicin Alone: On Cycle 1, Day 1, participants received doxorubicin 75 mg/m2 IV

  Olaratumab Alone: On Cycle 1, Day 10, participants received 20 mg/kg of olaratumab IV.

  Olaratumab + Doxorubicin:

  For Cycle 2, participants received 20 mg of olaratumab on Days 1 and 8 of each 21-day cycle, IV. On Day 1 of Cycle 2, doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion.

  For Cycles 3 - 8, Day 1 and 8, olaratumab 15 mg/kg was administered and on Day 1 doxorubicin 75 mg/m2 was administered IV immediately following the completion of the olaratumab infusion.

  Participants continued to receive olaratumab monotherapy (on days 1 and 8 of each cycle) for Cycle 9 onwards, until discontinuation criteria are met.

  Interventions:

  • Drug: Olaratumab
  • Drug: Doxorubicin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 31, 2018): 49
• Original Estimated Enrollment (submitted: December 22, 2014): 24
• Actual Study Completion Date: November 2, 2018
• Actual Primary Completion Date: May 20, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have histological or cytological evidence of a diagnosis of soft tissue sarcoma (STS) that is advanced and/or metastatic
• Have the presence of measurable and/or nonmeasurable disease
• Have given written informed consent prior to any study-specific procedures
• Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have discontinued previous treatments for cancer and recovered from the acute effects of therapy
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

• Have received treatment within 28 days of the initial dose of study drug with an investigational product or non-approved use of a drug or device for noncancer indications
• Have received prior treatment with doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
• Have active central nervous system (CNS) metastasis. Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids
• Have unstable hepatic disease with a grade equal to or greater than Child-Pugh B
• Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis
• Have a history of another primary cancer, with the exception of a) curatively resected nonmelanoma 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
• Have a history of chronic heart failure or left ventricular dysfunction
• Have a resting heart rate of less than (<)50 beats per minute (bpm) or greater than (>)100 bpm
• Have a history of radiation therapy involving the mediastinal/pericardial area. Previous radiation therapy is allowed but must not have included whole pelvis radiation

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: NCT02326025
• Other Study ID Numbers: 15676; I5B-EW-JGDI ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• 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: April 2019