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

NCT03283696 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 16430I5B-MC-JGDR2016-004287-19
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 6

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)

  A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: 1. Grade 3 or 4 febrile neutropenia, or sepsis., or 2. Grade 4 neutropenia lasting 7 days or longer. 3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage. 4. Nonhematologic Grade ≥3 toxicity, except for toxicities (such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea) that can be controlled with optimal medical management within 48 hours or clinically non-significant laboratory abnormalities.

  Cycle 1 (Up To 24 days)

Secondary Outcomes (10)

• Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab

  Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)

• PK: Maximum Serum Concentration (Cmax,ss) of Olaratumab at Steady-state

  Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)

• PK: Trough Serum Concentration (Cmin)

  Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)

• PK: Trough Serum Concentration (Cmin,ss) of Olaratumab at Steady-state

  Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)

• Number of Participants With Anti-Olaratumab Antibodies

  Baseline through Follow-up (Up To 21 Months)

Study Arms (1)

Olaratumab + Doxorubicin + Ifosfamide + Mesna

EXPERIMENTAL

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.

Drug: Olaratumab; Drug: Doxorubicin; Drug: Ifosfamide; Drug: Mesna

Interventions

Olaratumab DRUG

Administered IV

Also known as: LY3012207

Olaratumab + Doxorubicin + Ifosfamide + Mesna

Doxorubicin DRUG

Administered IV

Olaratumab + Doxorubicin + Ifosfamide + Mesna

Ifosfamide DRUG

Administered IV

Olaratumab + Doxorubicin + Ifosfamide + Mesna

Mesna DRUG

Administered per standard of care

Olaratumab + Doxorubicin + Ifosfamide + Mesna

Eligibility Criteria

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

You may qualify if:

• 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:
• have a negative serum pregnancy test at the time of enrollment,
• have a negative urine pregnancy test within 24 hours prior to the first dose of study treatment, and
• 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.

You may not qualify if:

• 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:
• curatively treated non-melanomatous skin cancer
• 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).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (6)

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

HELIOS Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Università degli Studi di Catania - Azienda Policlinico

Catania, 95123, Italy

Location

Related Links

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

MeSH Terms

Conditions

Sarcoma

Interventions

olaratumab; Doxorubicin; Ifosfamide; Mesna

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; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: September 14, 2017
• Study Start: October 18, 2017
• Primary Completion: April 29, 2019
• Study Completion: August 25, 2019
• Last Updated: September 10, 2020
• Results First Posted: September 10, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); US (2); DE (2)