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

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ClinicalTrials.gov Identifier: NCT03283696
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : November 5, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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).

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Drug: Olaratumab Drug: Doxorubicin Drug: Ifosfamide Drug: Mesna Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Olaratumab, Doxorubicin and Ifosfamide in the Treatment of Patients With Advanced or Metastatic Soft Tissue Sarcoma
Actual Study Start Date : October 19, 2017
Estimated Primary Completion Date : November 8, 2019
Estimated Study Completion Date : November 8, 2019


Arm Intervention/treatment
Experimental: Olaratumab + Doxorubicin + Ifosfamide + Mesna
Olaratumab, doxorubicin and ifosfamide plus mesna administered intravenously (IV).
Drug: Olaratumab
Administered IV
Other Name: LY3012207

Drug: Doxorubicin
Administered IV

Drug: Ifosfamide
Administered IV

Drug: Mesna
Administered per standard of care




Primary Outcome Measures :
  1. Number of Participants with Olaratumab Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (21 Days) ]
    Number of participants with olaratumab DLTs


Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Maximum Serum Concentration (Cmax,1) of Olaratumab [ Time Frame: Pre-Dose Day 8 of Cycle 1 through Pre-dose Day 1 Cycle 2 ]
    PK: Cmax of olaratumab

  2. PK: Trough Serum Concentration (Cmin,1) of Olaratumab [ Time Frame: Pre-Dose Day 8 of Cycle 1 through Pre-dose Day 1 Cycle 2 ]
    PK: Cmin of olaratumab

  3. PK: Maximum Serum Concentration (Cmax,ss) of Olaratumab [ Time Frame: Pre-Dose Day 8 of Cycle 3 through Pre-Dose Day 1 Cycle 4 ]
    PK: Cmax of olaratumab

  4. PK: Trough Serum Concentration (Cmin,ss) of Olaratumab [ Time Frame: Pre-Dose Day 8 of Cycle 3 through Pre-Dose Day 1 Cycle 4 ]
    PK: Cmin of olaratumab

  5. Number of Participants with Anti-Olaratumab Antibodies [ Time Frame: Baseline through Follow-up (Estimated up to 18 Months) ]
    Number of participants with anti-olaratumab antibodies

  6. Objective Response Rate (ORR): Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline up to Short-Term Follow-Up Period (Estimated up to 18 Months) ]
    ORR

  7. Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Disease Progression or Death Due to Any Cause (Estimated up to 18 Months) ]
    PFS

  8. Duration of Response (DoR) [ Time Frame: Date of Complete Response (CR) or Partial Response (PR) to Objective Disease Progression or Death Due to Any Cause (Estimated up to 18 Months) ]
    DoR

  9. Disease Control Rate (DCR): Proportion of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD) [ Time Frame: Baseline up to Short-Term Follow-up Period (Estimated up to 18 Months) ]
    DCR

  10. Overall Survival (OS) [ Time Frame: Baseline to Date of Death Due to Any Cause (Estimated up to 18 Months) ]
    OS



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283696


Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com

Locations
United States, Florida
University of Miami School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact    305-243-6102      
Principal Investigator: Jonathan C Trent         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact    713-792-3626      
Principal Investigator: Neeta Somaiah         
Germany
Universitätsklinikum Essen Recruiting
Essen, Nordrhein-Westfalen, Germany, 45122
Contact    4920172385558      
Principal Investigator: Sebastian Bauer         
HELIOS Klinikum Berlin-Buch Recruiting
Berlin, Germany, 13125
Contact    4930940154801      
Principal Investigator: Peter Reichardt         
Italy
Istituto Nazionale dei Tumori Recruiting
Milano, Lombardie, Italy, 20133
Contact    390223902182      
Principal Investigator: Silvia Stacchiotti         
Università degli Studi di Catania - Azienda Policlinico Recruiting
Catania, Italy, 95123
Contact    390953781496      
Principal Investigator: Hector Soto Parra         
Sponsors and Collaborators
Eli Lilly and Company
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

Additional Information:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03283696     History of Changes
Other Study ID Numbers: 16430
I5B-MC-JGDR ( Other Identifier: Eli Lilly and Company )
2016-004287-19 ( EudraCT Number )
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 1, 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Liposomal doxorubicin
Isophosphamide mustard
Olaratumab
Ifosfamide
Mesna
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Protective Agents
Physiological Effects of Drugs