A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma
Condition: Soft Tissue Sarcoma
MeSH terms: Sarcoma
Intervention: Olaratumab; Doxorubicin; Ifosfamide; Mesna
Intervention description: Administered IV; Administered IV; Administered IV; Administered per standard of care
Intervention MeSH terms: Doxorubicin; Ifosfamide; Olaratumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).
    

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.