Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Study to Evaluate the Efficacy and Safety of Pazopanib Monotherapy Versus Placebo in Women Who Have Not Progressed After First Line Chemotherapy for Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Brief Summary: This was a study to determine whether therapy with pazopanib was effective and safe in women with epithelial ovarian, fallopian tube, or primary peritoneal cancer whose cancer had not progressed on first line chemotherapy.


Options:
A: Inclusion criteria

1. Patients were diagnosed with ovarian cancer, fallopian tube cancer or primary peritoneal cancer confirmed by previous pathology, and the pathological type was non-mucinous adenocarcinoma.There were previous surgical wax preservation.
2. Initial platinum-resistant relapse, the recurrence time was less than 6 months after the last chemotherapy.
3. Complicated with malignant pleural effusion or ascites, or with recurrent lesions that can be evaluated clinically.
4. ECOG physical status score 0 or 1.
5. The expected survival time is ≥ 4 months.
6. In the previous treatment, there was no antivascular targeted therapy;
7. Patients without pleural effusion or ascites should be confirmed by CT or MRI according to the standard of RECIST1.1 version, requiring the patient to have at least one measurable focus as the target focus. If the target focus is a lymph node with a short diameter of more than 1.5 cm, and the target focus is not suitable for surgical treatment, the target focus has not received radiotherapy or relapsed in the radiotherapy field.
8. The baseline blood routine conforms to the following criteria:

   1. neutrophil count ≥ 1.5x109 /L;
   2. platelet count ≥ 100x109 PG L;
   3. hemoglobin ≥ 9g/dL (blood transfusion is allowed to achieve or maintain this target) .
9. Liver function meets the following criteria:

   1. total bilirubin\<1.5 normal limit (ULN);
   2. glutamic oxaloacetic transaminase (AST), glutamic pyruvic transaminase (ALT)\<2.5xULN, which is allowed\<5xULN in patients with liver metastasis.
10. Serum creatinine ≤ 1.25xULN or calculated creatinine clearance ≥ 50mL/min.

Exclusion criteria

1. Have received more than two chemotherapy regimens in the past.
2. Currently or recently (within 30 days before enrollment) using another research drug or participating in another clinical study.
3. other malignant tumors have occurred within 5 years (except adequately treated cervical carcinoma in situ or skin squamous cell carcinoma, or controlled basal cell carcinoma of the skin).
4. Patients with hypertension that cannot be reduced to normal range after antihypertensive treatment (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg).
5. Suffer from myocardial ischemia or myocardial infarction above II grade and poorly controlled arrhythmias (including QTc interval ≥ 470ms in females).
6. According to the NYHA standard, there were previous or present cardiac insufficiency of grade II or above, or color Doppler echocardiography showed that the left ventricular ejection fraction ((LVEF)) was less than 50% or the lower limit of the normal value.
7. Abnormal coagulation function (INR\>1.5 or prothrombin time (PT) \> ULN+4 seconds or APTT\>1.5xULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy.
8. There were significant clinical bleeding symptoms or definite bleeding tendency in the first 3 months, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood or above, or suffering from vasculitis.
9. Major surgical operations or severe traumatic injuries, fractures or ulcers occurred within the first 4 weeks of randomization.
10. There are significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction.
11. Urine routine indicates urinary protein ≥++, or confirms 24-hour urinary protein ≥ 1.0g.
12. The researchers judged other conditions that may affect the conduct of clinical studies and the determination of research results.
13. Allergic or heterogeneous reactions to doxorubicin and / or related substances.
14. The cumulative dose of doxorubicin (including previous anthracycline, if any) is expected to reach or exceed 550 mg after 4 courses of doxorubicin liposome injection treatment.
15. Uncontrollable arrhythmias or electrocardiograms abnormalities determined by the lead researcher to be at risk.
16. A history of doxorubicin liposome therapy in recent half a year.
17. Have previously received local radiotherapy of the pelvis or lower abdomen.
B: 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)
C: Inclusion Criteria:

* written informed consent
* At least 18 years old.
* Histologically confirmed, FIGO stage II-IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma that was treated with surgical debulking and at least five cycles of platinum-taxane doublet chemotherapy.
* Study randomization at least 3 weeks and not more than 12 weeks from the date of the last chemotherapy dose, and all major toxicities from the previous chemotherapy must have resolved.
* No evidence of disease progression
* ECOG status of 0 or 2
* Able to swallow and retain oral medication.
* Adequate hematologic, hepatic, and renal system function as follows:

Hematologic

* Absolute neutrophil count (ANC) at least 1.5 X 10\^9/L
* Hemoglobin at least 9 g/dL (or 5.59 mmol/L)
* Platelets at least 100 X 10\^9/L
* Prothrombin time (PT) or international normalized ratio (INR) up to 1.2 X ULN
* Activated partial thromboplastin time (aPTT) up to 1.2 X ULN Hepatic
* Total bilirubin up to 1.5 X ULN
* AST and ALT up to 2.5 X ULN Renal
* Serum creatinine up to 1.5 mg/dL

Or, if greater than 1.5 mg/dL:

Calculated creatinine clearance at least 50 mL/min Urine Protein

* Urine protein is 0, trace, or +1 determined by dipstick urinalysis, or \< 1.0 gram determined by 24- hour urine protein analysis.
* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception.

Exclusion Criteria:

* Either (a) bulky disease, or (b) any residual disease which in the opinion of the investigator will need imminent second-line therapy
* Synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless certain conditions are met.
* Clinically significant gastrointestinal abnormalities
* Prolongation of corrected QT interval (QTc) \> 480 msecs
* History of any one or more cardiovascular conditions within the past 6 months prior to randomization
* Cardiac angioplasty or stenting
* Myocardial infarction
* Unstable angina
* Symptomatic peripheral vascular disease

  * Class III or IV congestive heart failure
* Poorly controlled hypertension
* History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months prior to randomization
* Major surgery (including interval debulking) or trauma within 28 days, or minor surgical procedures within 7 days, prior to randomization, or has any non-healing wound, fracture, or ulcer.
* Evidence of active bleeding or bleeding diathesis.
* Hemoptysis within 6 weeks prior to randomization.
* Endobronchial metastases.
* Serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Investigational or anti-VEGF anticancer therapy prior to study randomization.
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib
* Invasive malignancies that showed activity of disease within 5 years prior to randomization
D: Inclusion Criteria:

1. Availability of volunteer for the entire study period and willingness to adhere to protocol requirements as evidenced by written informed consent.
2. Patients with metastatic breast cancer/advanced ovarian cancer having age within the range of between 18-55 years.
3. Subjects who had no evidence of underlying disease
4. Subjects who had signed written consent form

Exclusion Criteria:

1. Females who were pregnant, breastfeeding, or are likely to become pregnant
2. Subjects who had any medical condition (except metastatic breast cancer/advanced ovarian cancer) that could jeopardize their health or prejudice the results
3. Subjects deemed uncooperative or noncompliant
4. Smoking or consumption of any nicotine products

Answer: C