Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase 2 Trial Investigating Liposomal Doxorubicin With or Without Anti-Platelet Derived Growth Factor Receptor-Alpha (PDGFRα) Monoclonal Antibody IMC-3G3 in Patients With Platinum-Refractory or Platinum-Resistant Advanced Ovarian Cancer
Brief 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.


Options:
A: Inclusion Criteria:

1. Histologically confirmed, stage III or IV epithelial ovarian carcinoma
2. No previous treatment with chemotherapy or radiation therapy
3. All patients must have undergone cytoreductive surgery, with the

   following results:
   1. No residual tumor nodule \> 3cm
   2. No residual tumor involvement of the bowel (ie. invasion into bowel

      wall)
   3. No residual intestinal obstruction
4. Measurable or evaluable disease. Patients with elevated CA-125 levels

   and/or evaluable disease per RECIST criteria are eligible.
5. ECOG performance status 0 or 1.
6. ANC ≥ 1500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9.0 g/dL.
7. Total bilirubin ≤ 1.5 x upper limits of normal (ULN), ALT and AST ≤ 2.5 x

   ULN (≤ 5 x ULN for patients with liver metastases)
8. Serum creatinine _ 1.5 x ULN
9. INR \< 1.5 or a PT/PTT within normal limits. Patients receiving anticoagulation

   treatment with an agent such as warfarin or heparin may be

   allowed to participate. For patients on warfarin, the INR may be \> 1.5,

   and should be measured prior to initiation of sorafenib and monitored at

   least weekly until INR is stable in the desired therapeutic range.
10. Women of childbearing potential must have a negative serum pregnancy

    test performed within 7 days prior to start of treatment.
11. Patients must be able to understand the nature of this study and give

written informed consent.

Exclusion Criteria:

1. Age \< 18 years
2. Active cardiac disease, including: A) congestive heart failure \> class II

   NYHA , B) unstable angina or onset of angina within last 3 months, C) myocardial infarction within 6 months
3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
4. Patients with CNS metastases. Patients with neurological symptoms

   must undergo a CT scan/MRI of the brain to exclude brain metastasis.
5. Uncontrolled hypertension defined as systolic blood pressure \> 150mmHg or diastolic pressure \> 90mmHg, despite optimal medical management
6. Known HIV, chronic hepatitis B or chronic hepatitis C infections
7. Women who are pregnant or lactating. Women of childbearing potential

   must agree to use adequate contraception from time of study entry until

   at least 3 months after the last administration of study drug.
8. Active clinically serious infection (\> grade 2)
9. Thrombotic or embolic events such as cerebral vascular accident

   including transient ischemic attacks within the last 6 months.
10. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of

    starting treatment.
11. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of

    starting treatment
12. Serious non-healing wound, ulcer, or bone fracture
13. Evidence of history of bleeding diathesis or coagulopathy
14. Major surgery, open biopsy, or significant traumatic injury within 4 weeks

    of starting treatment.
15. Any condition that impairs the ability to swallow whole pills
16. Patients with any type of malabsorption
17. Known or suspected allergy to any of the agents used in this treatment
18. Use of St. John's Wort or rifampin
B: Inclusion Criteria:

* Patients must be ≥ 18 years of age.

  * Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.
  * Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).
  * Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation

For the penultimate chemotherapy course prior to enrolment on the study:

• Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy

For the last chemotherapy course immediately prior to randomisation on the study:

* Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, following completion of this chemotherapy course
* Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin) and have received at least 4 cycles of treatment
* Patients must be randomized within 8 weeks of their last dose of chemotherapy
* Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
* BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism" etc.)
* Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.
C: 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
D: Inclusion Criteria:

* with recurrent epithelial carcinoma of the ovary, fallopian tube or primary peritoneum
* At least 1 previous line of chemotherapy
* Measurable disease
* Patients have a normal organ and bone marrow function measured within 28 days of randomization
* WHO 0-2

Exclusion Criteria:

* Primary platinum-refractory disease
* Known hypersensitivity to olaparib
* Resting ECG with QTc \> 470 msec
* Concomitant use of known potent CYP3A4 inhibitors
* Symptomatic uncontrolled brain metastases
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication

Answer: C