A Study of Liposomal Doxorubicin With or Without Olaratumab (IMC-3G3) in Platinum-Refractory or Resistant Advanced Ovarian Cancer
Condition: Ovarian Neoplasms
MeSH terms: Ovarian Neoplasms
Intervention: Olaratumab; liposomal doxorubicin
Intervention description: 20 milligrams per kilogram (mg/kg) administered by intervenous (IV) infusion every 2 weeks (14 days). Treatment will continue until there is evidence of progressive disease (PD) or development of unacceptable toxicity; 40 milligrams per square meter (mg/m²) administered according to the manufacture's instructions every 4 weeks (28 days). Treatment will continue until there is evidence of PD or development of unacceptable toxicity
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Olaratumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liposomal Doxorubicin; IMC-3G3; 3G3; Platinum resistant; Platinum refractory; Ovary; Neoplasm; PDGFr

Summary:

      The purpose of this study is to determine if participants with platinum-refractory or
      platinum-resistant advanced ovarian cancer have a better outcome when treated with Olaratumab
      (IMC-3G3) in combination with Liposomal Doxorubicin than when treated with Liposomal
      Doxorubicin alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant has histologically or cytologically confirmed epithelial ovarian
             cancer, primary peritoneal carcinoma, fallopian tube cancer, or ovarian clear cell
             carcinoma

          -  The participant must have at least one of the following: a platinum-free interval of
             ≤12 months after the final dose of primary or subsequent platinum-based therapy
             (platinum-resistant), progression during primary or subsequent platinum-based therapy
             (platinum-refractory), or persistent radiographic disease after primary or subsequent
             platinum-based therapy (platinum-refractory)

          -  The participant has a pre-study echocardiogram or multigated acquisition (MUGA) scan
             with an actual left ventricular ejection fraction (LVEF) ≥50%, within 21 days prior to
             randomization

          -  The participant has at least one unidimensionally measurable target lesion [≥20
             millimeters (mm) with conventional techniques, or ≥10 mm by spiral computed tomography
             (CT) or magnetic resonance imaging (MRI)], as defined by Response Evaluation Criteria
             in Solid Tumors, Version 1.0 (RECIST v1.0) guidelines. Tumors within a previously
             irradiated field will be designated as "nontarget" lesions unless progression is
             documented or a biopsy is obtained to confirm persistence at least 90 days following
             completion of radiation therapy

          -  The participant has recovered to Grade ≤1 by the National Cancer Institute Common
             Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0) from the effects
             of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted
             therapies for ovarian cancer, with the exception of alopecia or peripheral neuropathy
             (which must have resolved to ≤Grade 2). The exceptions for such effects are allowed
             lab values of ≤Grade 2 specified elsewhere in these inclusion criteria

          -  The participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status
             score of ≤1 at study entry

          -  The participant has the ability to understand and the willingness to sign a written
             informed consent

          -  The participant has adequate hematological functions [absolute neutrophil count (ANC)
             ≥1200 cells/microliter (cells/μL), hemoglobin ≥9 grams/deciliter (g/dL), and platelets
             ≥100,000 cells/μL]

          -  The participant has adequate hepatic function as defined by total bilirubin ≤1.5 × the
             upper limit of normal (ULN), and aspartate transaminase (AST) and alanine transaminase
             (ALT) ≤3 × the ULN (or ≤5 × the ULN in the presence of known liver metastases)

          -  The participant has adequate renal function as defined by serum creatinine ≤1.5 × the
             institutional ULN. If creatinine is above the ULN, the participant's creatinine
             clearance is ≥60 milliliters/minute (mL/min)

          -  The participant has urinary protein ≤1+ on dipstick or routine urinalysis; if urine
             dipstick or routine analysis is ≥2+, a 24-hour urine for protein must demonstrate
             <1000 milligrams (mg) of protein to allow participation

          -  The participant must have adequate coagulation function as defined by International
             Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) ≤5seconds above
             ULN. Participants on anticoagulation must be on a stable dose of anticoagulant with a
             therapeutic INR and no active bleeding within 14 days prior to randomization, or on
             low molecular weight heparin AND have no pathological condition carrying a high risk
             of bleeding. Mild elevations of PTT of up to 1.5 × the ULN are acceptable, provided
             that, in the opinion of the investigator, they are related to ongoing use of coumarins
             [for example (e.g.), warfarin]

          -  The participant has a pre-study echocardiogram or MUGA scan with an actual LVEF ≥50%,
             within 21 days prior to randomization

          -  Women of childbearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control; abstinence) prior to randomization and for the
             duration of study participation

        Exclusion Criteria:

          -  The participant has brain metastases or leptomeningeal disease

          -  The participant received more than one biologic and/or more than one hormonal therapy,
             administered either concomitantly with platinum-based therapy or separately

          -  The participant has a history of treatment with other agents targeting platelet
             derived growth factor (PDGF) or PDGF receptor (PDGFR)

          -  The participant has an increased level of cancer antigen-125 (CA-125) in the absence
             of concomitant clinical or radiographic progression

          -  The participant has received radiotherapy, chemotherapy, or biologic therapy directed
             at the malignant tumor within 3 weeks prior to randomization, or hormonal therapy
             directed at the malignant tumor within 1 week prior to randomization. Continuation of
             hormone replacement therapy is permitted

          -  The participant has a suspected impending bowel obstruction (including partial
             obstruction), based on clinical or radiographic data

          -  The participant has a history of allergic reactions attributed to compounds of
             chemical or biologic composition similar to that of IMC-3G3

          -  The participant has an uncontrolled intercurrent illness including, but not limited
             to, ongoing or active infection requiring parenteral antibiotics, symptomatic
             congestive heart failure,uncontrolled hypertension, clinically significant cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  The participant has a history of another primary cancer, with the exception of: a)
             curatively resected nonmelanomatous skin cancer; b) curatively treated cervical
             carcinoma in-situ; or c) other primary solid tumor treated with curative intent and no
             known active disease present and no treatment administered during the last 3 years
             prior to randomization

          -  The participant is pregnant or lactating

          -  The participant has ongoing side effects ≥Grade 2 due to agents administered more than
             28 days prior to randomization. The exceptions for such effects are allowed lab values
             and toxicities of ≤Grade 2, specified in the inclusion criteria

          -  The participant has unstable angina pectoris, angioplasty, cardiac stenting, or
             myocardial infarction 6 months prior to randomization

          -  The participant has participated in clinical trials of experimental agents within 28
             days prior to randomization

          -  The participant has a history of uncontrolled hereditary or acquired bleeding or
             thrombotic disorders

          -  The participant has a serious or nonhealing active wound, ulcer, or bone fracture

          -  The participant has known human immunodeficiency virus positivity

          -  The participant had a major surgical procedure, an open biopsy, or significant
             traumatic injury within 28 days prior to randomization

          -  The participant has received an anthracycline for any indication in the past