Please select the eligibility criteria that correspond to the clinical trial below.
Title: N/A
Brief Summary: To study the efficacy and safety of intraperitoneal injection bevacizumab combined with intraperitoneal hyperthermic perfusion chemotherapy in treatment of malignant ascites of ovarian cancer. To analyze the clinical significance of the concentration change of vascular endothelial growth factor (VEGF) in ascites in treatment of intraperitoneal injection bevacizumab


Options:
A: Inclusion Criteria:

* Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements.
* Histologically confirmed and documented ovarian cancer with malignant ascites.
* ECOG(Eastern Cooperative Oncology Group, ECOG) PS 0-2.
* Life expectancy of \>3 months.
* No serious inadequate bone marrow function, liver and renal function or significant cardiovascular disease.

Exclusion Criteria:

* Known hypersensitivity to any of the study drugs or excipients.
* Any current anti-cancer therapy.
* No evidence of ascites.
* Key organ dysfunction.
* Significant cardiovascular disease (e.g. congestive heart failure (CHF), uncontrolled cardiac arrhythmia, angina, heart valve disease, myocardial infarction and refractory hypertension need to be long time controlled by medicine).
* Non-healing wound, ulcer or bone fracture.
* Uncontrolled psychiatric history.
B: Inclusion Criteria:

* Female patients ≥18 years of age.
* Patients with histologically confirmed epithelial ovarian or fallopian tube carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours
* Recurrence or progression at least 6 months after the last chemotherapy cycle of a first line carboplatin + paclitaxel chemotherapy including bevacizumab (recurrence or progression might occur either during or after bevacizumab as maintenance)
* Patients can be included if they have a RECIST progression, with either measurable or non-measurable disease
* ECOG (Eastern Cooperative Oncology Group Performance) Status of 0-2.
* Life expectancy of at least 12 weeks.
* Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient's awareness and willingness to comply with the study requirements including blood samples for molecular analyses.
* Availability of tumour samples for molecular analyses from primary surgery (mandatory) and secondary surgery (when available)

Exclusion Criteria:

Cancer related

* Ovarian tumours with low malignant potential (i.e. borderline tumours)
* History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met:

  * stage ≤Ia
  * no more than superficial myometrial invasion
  * no lymphovascular invasion
  * not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma).
* Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.

Prior current or planned treatment:

* More than one previous chemotherapy line
* Previous therapy with other anti-angiogenetic agents different from bevacizumab.
* Any prior radiotherapy to the pelvis or abdomen.
* Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose.Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (except for line patency, in which case international normalized ratio \[INR\] must be maintained below 1.5). Post operative prophylaxis with low molecular weight heparin sc is allowed.
* Current or recent (within 30 days of first study dosing) treatment with any other investigational drug.

Laboratory:

* Inadequate bone marrow function: ANC (absolute neutrophil count): \<1500/mm3, or platelet count \<100,000/mm3 or Haemoglobin \<9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9 g/dl.
* Inadequate coagulation parameters:

  * activated partial thromboplastin time (APTT) \>1.5 x upper limit of normal (ULN) or
  * INR (international normalized ratio) \>1.5
* Inadequate liver function, defined as:

  * serum (total) bilirubin \>1.5 x ULN for the institution
  * AST/SGOT or ALT/SGPT \> 2.5 x ULN.
* Inadequate renal function, defined as:

  * serum creatinine \>2.0 mg/dl or \>177 micromol/l
  * urine dipstick for proteinuria \>2+. Patients with ≥ 1+ proteinuria at baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in their 24-hour urine collection.

Prior or concomitant conditions or procedures:

* History or evidence of brain metastases or spinal cord compression.
* Pregnant or lactating females.
* History or evidence of thrombotic or haemorrhagic disorders; including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤6 months prior to the first study treatment).
* Uncontrolled hypertension (sustained systolic \>150 mm Hg and/or diastolic \>100 mm Hg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including:
* myocardial infarction or unstable angina within ≤6 months prior to the first study treatment
* New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF)
* serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia)
* peripheral vascular disease ≥grade 3 (i.e. symptomatic and interfering with activities of daily living requiring repair or revision).
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess, or with signs of impending bowel obstruction within 6 months prior to the first study treatment.
* Non-healing wound, ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations.
* Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer, etc.), physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
C: Inclusion Criteria:

* Female 18 years of age or older at the time the written informed consent is obtained
* Gynecologic Oncology Group (GOG) Performance Status of 0 or 1
* Life expectancy \>= 3 months (per investigator opinion)
* Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (Subjects with pseudomyxoma , mesothelioma, unknown primary tumor, sarcoma, or neuroendocrine histology, with borderline ovarian cancer, ie, subjects with low malignant potential tumors, and with clear cell or mucinous histology are excluded)
* Subjects must have undergone surgery for ovarian cancer, primary peritoneal cancer, or fallopian tube cancer including at least a unilateral oophorectomy
* Radiologically evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with modifications
* Subjects must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, high-dose therapy, consolidation therapy, bevacizumab or extended therapy administered after surgical or non-surgical assessment.
* Adequate organ and hematological function
* Generally well controlled blood pressure with systolic blood pressure \<= 140 mmHg and diastolic blood pressure \<= 90 mmHg prior to randomization. The use of anti-hypertensive medications to control hypertension is permitted
* Radiographically documented disease progression either on or following the last dose of prior chemotherapy regimen for epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

Exclusion Criteria:

* Subjects who have received more than 3 previous regimens of anti-cancer therapy for epithelial ovarian, primary peritoneal or fallopian tube cancers
* Subjects who have received paclitaxel as consolidation therapy, maintenance, or monotherapy are excluded
* Subjects with primary platinum-refractory disease
* Subjects with platinum-free interval (PFI) \> 12 months from their last platinum based therapy
* Radiotherapy \<= 14 days prior to randomization. Subjects must have recovered from all radiotherapy-related toxicities
* Previous abdominal or pelvic radiotherapy
* History of arterial or venous thromboembolism within 12 months prior to randomization
* History of clinically significant bleeding within 6 months prior to randomization
* History of central nervous system metastasis
* Has not yet completed a 21 day washout period prior to randomization for any previous anti cancer systemic therapies (30 days for prior bevacizumab)
* Enrolled in or has not yet completed at least 30 days (prior to randomization) since ending other investigational device or drug, or currently receiving other investigational treatments
* Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 \>= Grade 2 in severity except alopecia
* Known active or ongoing infection (except uncomplicated urinary tract infection \[UTI\]) within 14 days prior to randomization
* Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
* Treatment within 30 days prior to randomization with strong immune modulators including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, and lenalidomide
* Clinically significant cardiovascular disease within 12 months prior to randomization
* Major surgery within 28 days prior to randomization or still recovering from prior surgery
* Minor surgical procedures, except placement of tunneled central venous access device within 3 days prior to randomization. Diagnostic laparoscopy is regarded as a minor surgical procedure.
D: 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

Answer: A