A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma
Condition: Soft Tissue Sarcoma
MeSH terms: Sarcoma
Intervention: Olaratumab; Doxorubicin; Placebo
Intervention description: Administered IV; Administered IV; Administered IV
Intervention MeSH terms: Doxorubicin; Olaratumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 509.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: leiomyosarcoma; soft tissue sarcoma (STS); advanced soft tissue sarcoma; metastatic soft tissue sarcoma; liposarcoma; undifferentiated pleomorphic sarcoma; doxorubicin

Summary:

      The main purpose of this study is to evaluate the efficacy of the combination of doxorubicin
      plus the study drug known as olaratumab versus doxorubicin plus placebo in participants with
      advanced or metastatic soft tissue sarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of advanced unresectable or metastatic soft tissue
             sarcoma not amenable to curative treatment with surgery or radiotherapy. Participants
             with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded.
             Note: Evidence of disease progression is required for participants that are not newly
             diagnosed.

          -  Presence of measurable or nonmeasurable but evaluable disease as defined by the
             Response Evaluation Criteria in Solid Tumors (RECIST 1.1, Eisenhauer et al. 2009).

          -  Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.

          -  The participant has not received any previous treatment with anthracyclines.

          -  The participant may have had any number of prior systemic cytotoxic therapies for
             advanced/metastatic disease and are considered appropriate candidates for
             anthracycline therapy. All previous anticancer treatments must be completed ≥ 3 weeks
             (21 days) prior to first dose of study drug.

          -  Availability of tumor tissue is required for study eligibility. The participant must
             have consented to provide archived formalin-fixed paraffin embedded (FFPE) tumor
             tissue or be subject to a pre-treatment re-biopsy of primary or metastatic tumor
             tissue for future central pathology review and translational research (if archived
             tissue is unavailable).

          -  Adequate hematologic, organ, and coagulation within 2 weeks (14 days) prior to
             randomization.

          -  Left ventricular ejection fraction (LVEF) ≥50% assessed within 28 days prior to
             randomization.

          -  Females of child-bearing potential must have a negative serum pregnancy test within 7
             days prior to randomization.

          -  Females of child-bearing potential and males must agree to use highly effective
             contraceptive precautions during the trial and up to 3 months following the last dose
             of study drug.

          -  The participant has, in the opinion of the investigator, a life expectancy of at least
             3 months.

        Exclusion Criteria:

          -  Diagnosis of GIST or Kaposi sarcoma.

          -  Active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at
             the time of randomization. Participants with a history of a CNS metastasis previously
             treated with curative intent (for example, stereotactic radiation or surgery) that
             have 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 randomization to rule out brain metastasis.

          -  Prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines
             or anthracenediones; the participant has received treatment with olaratumab or has
             participated in a prior olaratumab trial.

          -  Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.

          -  The participant has symptomatic congestive heart failure (CHF), left ventricular
             dysfunction (LVEF < 50%), severe myocardial insufficiency, cardiac arrhythmia, or
             cardiomyopathy.

          -  The participant has unstable angina pectoris, angioplasty, cardiac stenting, or
             myocardial infarction within 6 months of randomization.

          -  The participant has a QT interval calculated using Bazett's formula (QTcB) interval of
             >450 milliseconds (msec) for males and >470 msec for females on screening
             electrocardiogram (ECG).

          -  Females who are pregnant or breastfeeding.

          -  Known allergy to any of the treatment components including a history of allergic
             reactions attributed to compounds of chemical or biological composition similar to
             olaratumab.

          -  The participant has a known active fungal, bacterial, or viral infection including
             human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not
             required).