Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Study to Evaluate Efficacy and Safety of Pazopanib Monotherapy in Asian Women Who Have Not Progressed After First-line Chemotherapy for Advanced Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma - An Extension Study to VEG110655
Brief Summary: This is a study to determine whether therapy with pazopanib is effective and safe in Asian women with epithelial ovarian, fallopian tube or primary peritoneal cancer whose cancer has not progressed on first-line chemotherapy.


Options:
A: Inclusion Criteria:

* First diagnosis of histological confirmed (cytology alone excluded) epithelial ovarian cancer, fallopian tube or primary peritoneal cancer. Histology should be obtained by laparoscopy (or by laparotomy),
* FIGO-Stages IIIC - IV,
* ECOG performance status \< 2,
* Life expectancy of at least 6 months,
* Primary debulking surgery denied and maximum surgical effort of cytoreduction with the goal of no residual disease planned as interval debulking surgery,
* Interval between diagnosis and enrolment (informed consent) ≤ 8 weeks,
* Adequate hepatic, renal and bone marrow functions:

Platelets \> 100 000 /μL, Hemoglobin \> 9.0 g/dL, Absolute Neutrophil Count (ANC) \> 1500/μL, Prothrombin time and/or partial thromboplastin time \< 50% deviation from normal limits in the absence of therapeutic anticoagulation, Proteinuria \< CTCAE grade 2, Total bilirubin ≤ upper limit of normal (ULN), ALT and/or AST ≤ 2.5 x ULN, Glomerular filtration rate \>40 mL/min,

* Females, age 18 years or older,
* Patient has given written informed consent,

Exclusion Criteria:

* Histological diagnosis of malignant tumour of non-epithelial origin (e.g. germ cell tumour, malignant mixed mullerian tumour, sex cord-stromal tumour) of the ovary, the fallopian tube or peritoneum or borderline tumour of the ovary (tumour of low malignant potential),
* Non-healing wound, ulcer (intestinal tract, skin) or bone fracture,
* Clinical symptoms or signs of gastrointestinal obstruction,
* History of major thromboembolic event, defined as:

  * Pulmonary embolism (PE) within 6 months prior to enrolment,
  * Recurrent pulmonary embolism (history of at least 2 events),
* History of at least 2 unprovoked (without a transient or reversible risk factor) events of proximal deep venous thrombosis,
* Prior thrombosis or thromboembolic event in the presence of an inherited coagulopathy (including deficiency of antithrombin, deficiency of protein C or protein S, Factor V Leiden mutation, Prothrombin G20210A mutation),
* Patients with perioperative thrombosis including proximal deep vein thrombosis (DVT) or thrombosis of visceral vessels not associated with pulmonary embolism may be included in the trial if stable therapeutic anticoagulation is documented,
* Known inherited or acquired bleeding disorder,
* Significant cardiovascular diseases, including:

  * Hypertension not controlled by medical therapy,
  * Unstable angina within the past 6 months,
  * History of myocardial infarction within the past 6 months,
  * Congestive heart failure \> NYHA II,
  * Clinically relevant cardiac arrhythmia
* Peripheral vascular disease Fontaine stage ≥3,
* Clinically relevant pericardial effusion (e.g. pericardial effusion with echocardiographic or clinical signs of haemodynamic impairment),
* History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months,
* Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy, including HIV-infection, hepatitis B and/or C infection,
* Poorly controlled diabetes mellitus or other contraindication to high dose corticosteroid therapy,
* Clinical symptoms of brain metastases and/or diagnosis of brain metastases on imaging,
* Pre-existing sensory or motor neuropathy CTCAE ≥ 2, except due to trauma,
* Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug,
* Other malignancy diagnosed within the past 5 years, except:

  * non-melanomatous skin cancer (if adequately treated),
  * cervical carcinoma in situ (if adequately treated),
  * carcinoma in situ of the breast (if adequately treated),
  * prior or synchronous endometrial cancer (if adequately treated), provided the following criteria are met:

    * Disease stage FIGO ≤ IB,
    * No more than superficial myometrial invasion,
    * Not poorly differentiated (less than grade 3, no papillary serous or clear cell histology),
* Prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy),
* Prior radiotherapy to the abdomen or prior radiotherapy to an extra-abdominal target volume that would bear the risk of increased toxicity of chemotherapy,
* Hypersensitivity to Vargatef® (Nintedanib) and/or the excipients of the trial drugs,
* Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease, active ulcers (gastrointestinal tract, skin) or a laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study,
* Patients with preserved reproductive capacity who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner) during the trial and for at least twelve months after end of active therapy,
* Pregnancy or breast feeding,
* Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule,
* Active alcohol or drug abuse,
* Any contraindications for therapy with paclitaxel or carboplatin, e.g. a history of severe hypersensitivity reactions to paclitaxel or platinum-containing compounds and their excipients, or other drugs formulated with Polyoxyl 35 Castor Oil - ELP,
* Treatment with other investigational drugs or participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial.
B: The following eligibility criteria pertain to patients enrolling into PART 2 of the study:

Inclusion:

* Have a histologically confirmed diagnosis of high grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Received at least 3 prior chemotherapy regimens. Non-chemotherapy regimens and maintenance therapies administered as single agent treatment will not count as a chemotherapy regimen
* Relapsed/progressive disease as confirmed by CT scan
* Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA mutation
* Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses

Exclusion:

* History of prior cancers except for those that have been curatively treated, with no evidence of cancer currently (provided all chemotherapy was completed \>6 months prior and/or bone marrow transplant \>2 years prior to first dose of rucaparib).
* Prior treatment with any PARP inhibitor
* Symptomatic and/or untreated central nervous system metastases
* Pre-existing duodenal stent and/or any other gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
* Hospitalization for bowel obstruction within 3 months prior to enrollment
C: Inclusion Criteria:

A patient will be eligible for inclusion only if all of the following criteria are fulfilled:

1. Recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer (platinum sensitivity defined as no recurrence within 6 months of last receipt of platinum/chemotherapy).
2. High-grade serious or high-grade endometrioid histology.
3. Patient consents to perform HRD test.

   * Patients with known BRCA status: BRCA positive patients must submit the tissue for HRD test, though these patients need not to wait for HRD test results and can be randomized in HRD positive stratum.
   * If tumor tissue is not sufficient to perform HRD test: these patients shall be randomized in HRD negative stratum as HRD unknown.
4. Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.

   * No limits on number of platinum-based therapies. Population of patients who has previously received ≥ 3 lines of therapy for relapsed disease will be capped at 40%.
   * Up to one non-platinum-based line of therapy in recurrent setting.
   * Patients who are treated with bevacizumab just prior to entering in the trial must not have progressed under or within 3 months after bevacizumab.
   * Patients may have participated in a PARP inhibitor trial as first-line maintenance therapy and have not progressed within 3 months after PARP/placebo. Patients who received PARP inhibitor after relapse (definitive or maintenance therapy) are not eligible.
5. Target group: Age 18+
6. Histological confirmed ovarian, fallopian tube or peritoneal cancers
7. Patients must give informed consent
8. Patients may have undergone primary or interval debulking surgery
9. Patients may have received bevacizumab though no other prior use of anti-angiogenic therapy
10. Patients may have received a PARP inhibitor as first-line maintenance therapy.
11. Patients must have disease that is measurable according to RECIST or assessable according to the GCIG criteria
12. The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
13. ECOG performance status 0-2
14. Adequate organ function

    * Absolute neutrophil count (ANC) ≥1,5 x 109/L
    * Platelets \>100 x 109/L
    * Hemoglobin ≥ 9g/dl
    * Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Cockcroft-Gault formula
    * Total bilirubin ≤1.5x ULN
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN.
15. Able to take oral medications
16. Life expectancy of at least 12 weeks
17. Patients must fulfill all inclusions criteria and according to investigator fit to receive niraparib and/or bevacizumab.
18. Women of childbearing potential must use adequate birth control for the duration of study participation

Exclusion Criteria:

A patient will not be eligible for inclusion if any of the following criteria are fulfilled:

1. Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers and cancer types not mentioned in the inclusion criteria
2. Concurrent cancer therapy
3. Concurrent treatment with an investigational agent or participation in another clinical trial
4. Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
5. Previous malignant disease: patients are not eligible for the study if diagnosis, detection or treatment of invasive cancer (other than ovarian cancer; with the exception of basal or squamous cell carcinoma of the skin that was definitively treated) was detected within 2 years prior to randomization
6. Active infections or other serious underlying significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study
7. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
8. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
9. Known contraindications to PARP inhibitors or VEGF directed therapy
10. Known uncontrolled hypersensitivity to the investigational drugs
11. History of major thromboembolic event defined as:

    * Uncontrolled pulmonary embolism (PE)
    * Deep venous thrombosis (DVT)
    * Other related conditions, though patients with stable therapeutic anticoagulation for more than three months prior randomization are eligible for this study. This also apply to PE \& DVT.
12. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months
13. History of clinically significant hemorrhage in the past 3 months
14. Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (Dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization)
15. Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure \> NYHA III, severe peripheral vascular disease, QT prolongation \>470 msec ,clinically significant pericardial effusion
16. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards.
17. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels
18. Active or chronic hepatitis C and/or B infection
19. Persistence of clinically relevant therapy related toxicity from previous chemotherapy
20. Proteinuria as demonstrated by: (a) urine protein: creatinine (UPC) ratio \>/= 1.0 at screening OR (b) urine dipstick for proteinuria \>/=2+ (patients discovered to have \>/=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hr urine collection and must demonstrate \</=1g of protein in24 hours to be eligible
21. Patients must not have any known history of MDS
22. Patients must not have known persistent (\> 4 weeks) ≥ Grade 2 hematological toxicity from prior cancer therapy
23. Patients must not have known ≥ Grade 3 thrombocytopenia or anemia with the last chemotherapy regimen.
D: Inclusion Criteria:

* written informed consent
* At least 18 years old.
* Histologically confirmed, International Federation of Gynecology and Obstetrics (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
* Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 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
* 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.
* Prior or concurrent invasive malignancies that currently or within the last 5 years show/ed activity of disease (except ovarian, fallopian tube, or peritoneal cancer, or concurrent endometrial cancer FIGO stages IA/B)

Answer: D