A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma

NCT ID: NCT03283696

Last Updated: 2020-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-18
• Study Completion Date: 2019-08-25

Brief Summary

The purpose of this study is to evaluate the safety of ifosfamide when added to the combination regimen of olaratumab and doxorubicin in participants with advanced or metastatic soft tissue sarcoma (STS).

Conditions

Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Olaratumab + Doxorubicin + Ifosfamide + Mesna

Olaratumab 15 milligrams per kilogram (mg/kg) on Days 1 and 8 of a 21-day cycle, in combination with doxorubicin and ifosfamide was administered. When the safety of the 15-mg/kg dose of olaratumab was established, a 20-mg/kg loading dose cycle of olaratumab on Days 1 and 8 of a 21-day cycle in Cycle 1 only, followed by 15 mg/kg on Days 1 and 8 of subsequent cycles in combination with doxorubicin and ifosfamide plus mesna, was administered.

Group Type: EXPERIMENTAL

Olaratumab

Intervention Type: DRUG

Administered IV

Doxorubicin

Intervention Type: DRUG

Administered IV

Ifosfamide

Intervention Type: DRUG

Administered IV

Mesna

Intervention Type: DRUG

Administered per standard of care

Interventions

Olaratumab

Administered IV

Intervention Type: DRUG

Doxorubicin

Administered IV

Intervention Type: DRUG

Ifosfamide

Administered IV

Intervention Type: DRUG

Mesna

Administered per standard of care

Intervention Type: DRUG

Other Intervention Names

LY3012207

Eligibility Criteria

Inclusion Criteria

• Have a histological diagnosis of advanced STS (by local pathology review), for which treatment with doxorubicin, ifosfamide and mesna is deemed appropriate by the investigator.
• Have measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• Have adequate hematologic, organ and coagulation function within 2 weeks (14 days) prior to enrollment.
• Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group scale.
• Have received no prior lines of systemic therapy and are suitable to receive doxorubicin, ifosfamide and mesna. All previous anticancer treatments must have completed ≥3 weeks (21 days) prior to the first dose of study treatment.
• Have left ventricular ejection fraction (LVEF) ≥50% assessed within 28 days prior to enrollment.
• Have resolution of Adverse Events (AEs), with the exception of alopecia, and of all clinically significant toxic effects of prior locoregional therapy, surgery or radiotherapy to ≤Grade 1, by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.
• Have sufficient available material from archived formalin-fixed paraffin-embedded tumor tissue for biomarker-related studies. If such tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion must be performed.
• If male, must be sterile or agree to use an effective method of contraception or a highly effective method of contraception during the study and for at least 12 weeks following the last dose of study treatment.
• If female and of child-bearing potential, must:

1. have a negative serum pregnancy test at the time of enrollment,

2. have a negative urine pregnancy test within 24 hours prior to the first dose of study treatment, and

3. agree to use a highly effective method of contraception during the study and for 3 months following the last dose of study treatment.

• Have a life expectancy of at least 3 months, in the opinion of the investigator.

Exclusion Criteria

• Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have participated within the past 30 days in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed.
• Have previously completed or withdrawn from any study investigating olaratumab.
• Have received prior treatment with olaratumab, doxorubicin, or ifosfamide, or have participated in other trials investigating olaratumab.
• Have received prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.
• Have known urinary outflow obstruction, or inflammation of the urinary bladder (cystitis).
• Are diagnosed with gastrointestinal stromal tumor or Kaposi sarcoma.
• Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of CNS metastasis (previously treated with curative intent [for example, stereotactic radiation or surgery]) that has not progressed on follow-up imaging, have been asymptomatic for at least 60 days, and are not receiving systemic corticosteroids and/or anticonvulsants are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis.
• Have a history of another primary malignancy, with the exception of:

1. curatively treated non-melanomatous skin cancer

2. curatively treated cervical carcinoma in situ

• Have an active fungal, bacterial and/or known viral infection including human immunodeficiency virus or viral (A, B, or C) hepatitis (screening is not required).
• Have Grade 3 or 4 peripheral neuropathy per NCI-CTCAE Version 4.0.
• Have a serious cardiac condition.
• Have a resting heart rate of >100 beats per minute (bpm).
• Have a Fridericia's QT corrected interval (QTcF) interval of >450 milliseconds (msec) for males and >470 msec for females on screening electrocardiogram (ECG) utilizing Fridericia's correction.
• Have uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics.
• Have a psychiatric illness/social situation that would limit compliance with study requirements.
• Have electively planned or will require major surgery during the course of the study.
• Are females who are pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

University of Miami School of Medicine

Miami, Florida, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

HELIOS Klinikum Berlin-Buch

Berlin, , Germany

Istituto Nazionale dei Tumori

Milan, Lombardy, Italy

Università degli Studi di Catania - Azienda Policlinico

Catania, , Italy

Countries

United States; Germany; Italy

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.lillytrialguide.com/en-US/studies/soft-tissue-sarcoma/JGDR#?postal=

A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma

Other Identifiers

I5B-MC-JGDR

Identifier Type: OTHER

Identifier Source: secondary_id

2016-004287-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16430

Identifier Type: -

Identifier Source: org_study_id