Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study of AMG 386 With Paclitaxel and Carboplatin as First-line Treatment of Subjects With FIGO Stage III-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers
Brief Summary: The purpose of this study is to determine whether AMG 386 or AMG 386 Placebo in combination with Paclitaxel and Carboplatin are effective in the treatment of ovarian cancer.


Options:
A: Inclusion Criteria:

* Female aged ≥ 18 years at inclusion
* Histologically confirmed diagnosis of ovarian Sex cord-stromal tumors including the following cell types: granulosa cell tumours (adults and juveniles types), granulosa cell-theca cell tumour, Sertoli-Leydig cell tumours, malignant steroid cell tumours, gynandroblastoma, unclassified SCST and mixed tumours
* Documented relapse of SCST defined by progression of disease (radiologic, clinic or biological progression)
* At least one measurable site of disease as defined by RECIST 1.1

  * Tumours within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence \> 90 days following completion of radiotherapy.
* Patients must have been pre-treated with at least 1 prior line of platinum-based chemotherapy
* Adequate bone marrow, liver and renal functions including the following:

  * Absolute neutrophil count ≥ 1.5 G/L, platelet count ≥ 100 G/L, and hemoglobin ≥ 9 g/dL. Prior transfusion is authorized to keep haemoglobin level to ≥9g/dL
  * AST/ALT ≤ 3 x upper limit of normal (ULN) (or ≤ 5.0 ULN if liver metastasis) and total bilirubin ≤ 1.5 ULN
  * Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance ≥ 50 mL/min according to Cockcroft formula (or to MDRD formula for patients older than 65 years-old).
* Adequate coagulation panel:

  * PT ≤ 1.2 ULN
  * aPTT ≤ 1.5 ULN
  * INR ≤ 1.5 ULN
* Adequate neurologic function: only neuropathy (sensory and motor) grade ≤ 1 (CTCAE v4.3) are allowed
* ECOG Performance status of 0, 1, or 2 (Appendix 5)
* Life expectancy ≥ 4 months
* Satisfactory cardiac function
* Ability to understand and sign informed consent and willingness to comply with the study procedures before study entry
* Women of childbearing potential\* are required to have a negative serum pregnancy test within 7 days prior to study treatment initiation (i.e. Cycle 1 Day 1) and are willing to use adequate contraceptive method during the whole study period and for up to 6 months after the last treatment intake

  \*: Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential:
  * ≥ 50 years old and naturally amenorrheic for ≥ 1 year
  * Permanent premature ovarian failure confirmed by a specialist gynaecologist

    * Previous bilateral salpingo-oophorectomy or hysterectomy
    * XY genotype, Turner's syndrome, or uterine agenesis
    * Female patient who do not meet at least of the above criteria are defined as women of childbearing potential
* Covered by a medical insurance (in country where applicable)

Exclusion Criteria:

* Prior systemic therapy with bevacizumab
* Active peripheral neuropathy ≥ grade 3 (NCI-CTCAE v4.3)
* Prior history of other malignancies other than ovarian SCST (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the subjects has been free of the disease for at least 3 years or 5 years for breast cancer
* No resolution of specific toxicities related to any prior anti-cancer therapy to grade ≤1, excluding alopecia, according to the NCI-CTCAE v.4.3
* History or evidence of thrombotic or hemorrhagic disorders, including cerebro-vascular accident/stroke or transient ischemic attack or sub-arachnoids' haemorrhage within 6 months prior to first dose of study drugs
* Uncontrolled arterial hypertension (systolic ≥ 150 mmHg or diastolic ≥ 100 mmHg) despite optimal antihypertensive therapy or clinically significant cardiovascular disease including one of the following:

  * Myocardial infarction or instable angina within 6 months prior to first dose of study drugs
  * NYHA grade ≥ II congestive heart failure
  * Serious cardiac arrhythmia requiring medication
  * Peripheral vascular disease ≥ grade 3
* History of bowel obstruction, including sub-occlusive syndrome and history of abdominal fistula, gastro-intestinal perforation or intra-abdominal abscess during the year prior to inclusion
* Prior treatments:

  * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study inclusion or anticipation of need for major surgical procedure during the course of the study
  * Current or recent treatment with another investigational drug within 30 days of first study treatment dosing or within 6 weeks in case of prior nitrozo-urea and or mitomycin C treatment. In case of hormonotherapy , patients will be eligible if hormonotherapy is discontinued within at least 1 week before treatment initiation
  * Current or recent (within 10 days prior to randomization) chronic use of aspirin\> 325 mg/day or use of any other inhibitor of platelet aggregation
  * Chronic treatment (i.e. \> 15 days) with non steroids anti-inflammatory agents unless a washout period of 15 days was observed before the inclusion.
  * Intake of granulocyte growth factor within 3 weeks before study entry
* Presence of hematuria and proteinuria ≥ 2+ (urine dipstick). Patients with ≥ 2+ proteinuria on dipstick at screening should undergo a 24-hour urine collection and will be eligible only if 24-h proteinuria ≤ 1 g
* Untreated evolutive brain metastases
* Active bacteria or fungal infection (grade ≥2, CTC AE V4.3)
* Known HIV1, HIV2 or chronic hepatitis B or C infection
* Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies
* Any contraindications to paclitaxel treatment: for example severe hypersensitivity reactions to paclitaxel, macrogolglycerol ricinoleate (polyoxyl castor oil) or to any of the excipients (Ethanol Citric acid) (refer to Taxol® SPC for further details)
B: Inclusion Criteria:

* Signed Informed Consent Form
* Age ≥ 18 years
* Documented ovarian, primary peritoneal, or fallopian tube carcinoma that has recurred
* No prior chemotherapy in the recurrent setting
* Measurable disease
* Recovered from prior radiation therapy or surgery

Exclusion Criteria:

* Prior chemotherapy treatment for recurrent ovarian, primary peritoneal, or fallopian tube carcinoma
* History of abdominal fistula, gastrointestinal perforation (GIP), or intra-abdominal abscess
* Patients with clinical symptoms or signs of gastrointestinal (GI) obstruction or who require parenteral hydration, parenteral nutrition, or tube feeding
* Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
* Current, recent, or planned participation in an experimental drug study
* History of systemic bevacizumab (Avastin) or other vascular endothelial growth factor (VEGF) or VEGF receptor-targeted agent use
* Inadequately controlled hypertension
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association Class II or greater congestive heart failure (CHF)
* History of myocardial infarction or unstable angina
* History of stroke or transient ischemic attack (TIA)
* Known central nervous system (CNS) disease except for treated brain metastasis
* Significant vascular disease or recent peripheral arterial thrombosis
* History of hemoptysis
* Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
C: Inclusion Criteria:

* Female subjects 18 years of age or older with FIGO Stages III-IV epithelial ovarian, primary peritoneal or fallopian tube cancer with an indication for first-line treatment with paclitaxel and carboplatin x 6 cycles (Subjects with pseudomyxoma, mesothelioma, adenocarcinoma with an unknown primary tumour, carcinosarcoma, sarcoma, mucinous or neuroendocrine histology are excluded
* Subjects with FIGO Stage IIIA or IIIB disease must have undergone PDS for ovarian, primary peritoneal or fallopian tube cancer within 12 weeks prior to randomization
* Subjects with FIGO Stage IIIC or IV disease must either:
* Undergo PDS for epithelial ovarian, primary peritoneal or fallopian tube cancer within 12 weeks prior to randomization or
* Plan to have IDS following 3 cycles of paclitaxel and carboplatin plus AMG 386 or AMG 386 placebo for biopsy proven epithelial ovarian, primary peritoneal or fallopian tube cancer
* ECOG performance status of 0 or 1
* Adequate bone marrow, renal and hepatic function

Exclusion Criteria:

* Prior use of any anticancer therapy or experimental therapy for epithelial ovarian, primary peritoneal or fallopian tube cancer
* Previous abdominal and/or pelvic external beam radiotherapy
* History of central nervous metastasis
* History of arterial or venous thromboembolism within 12 months prior to randomization
* Clinically significant cardiovascular disease within 12 months prior to randomization
D: Inclusion Criteria:

* Must be at least 18 years old
* Must have measurable or detectable ovarian, fallopian or primary peritoneal cancer
* Must have been treated previously with carboplatin, cisplatin or another organoplatinum compound

Exclusion Criteria:

* Women who are pregnant or nursing
* History of congenital long QT syndrome
* Active bleeding or at risk of a bleeding disorder
* Other significant medical condition or history of medical condition which may put the patient at risk

Answer: C