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

NCT02326025 | Completed Phase 1 Results

• 2 other identifiers: 15676I5B-EW-JGDI
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 6

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.

Conditions

Sarcoma, Soft Tissue

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics (PK): Area Under The Concentration Curve Zero to Infinity (AUC[0-∞]) Doxorubicin

  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

  C1 and C2, D1: Predose, 0.5, 1, 2, 4, 8, 24, 48, 72, 96 Hrs Post dose

Secondary Outcomes (6)

• PK:Time of Maximum Observed Concentration (Tmax) Doxorubicin

  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

  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: Cmax Olaratumab

  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: Tmax Olaratumab

  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

• Percentage of Participants With Olaratumab Antibodies

  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

Study Arms (2)

Part A

EXPERIMENTAL

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.

Drug: Olaratumab; Drug: Doxorubicin

Part B

EXPERIMENTAL

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.

Drug: Olaratumab; Drug: Doxorubicin

Interventions

Olaratumab DRUG

Administered IV

Also known as: LY3012207, IMC-3G3

Part A; Part B

Doxorubicin DRUG

Administered IV

Part A; Part B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (6)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

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

ClinicalTrials.gov@lilly.com

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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2014
• First Posted: December 25, 2014
• Study Start: January 22, 2015
• Primary Completion: May 20, 2015
• Study Completion: November 2, 2018
• Last Updated: November 21, 2019
• Results First Posted: November 21, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)