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

This is an interventional treatment trial for Soft Tissue Sarcoma Read More

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.