Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Phase II Study of Pazopanib and Weekly Paclitaxel in Patients With Platinum Resistant/Refractory Ovarian Cancer Who Relapse During Bevacizumab Maintenance
Brief Summary: Study of Pazopanib and weekly Paclitaxel in patients with platinum resistant/refractory ovarian cancer who relapse during bevacizumab maintenance.


Options:
A: Inclusion Criteria:

* Female patients with newly diagnosed, histologically confirmed, high risk advanced (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer and / or fallopian - tube cancer who have completed first line platinum based chemotherapy (intravenous or intraperitoneal).
* Stage III patients must have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery.
* 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 completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation:
* Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study.
* Patients must be randomized within 8 weeks of their last dose of chemotherapy

Exclusion Criteria:

* BRCA1 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 with early stage disease (FIGO Stage I, IIA, IIB or IIC)
* Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment.
* Patients where more than one debulking surgery has been performed before randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and interval debulking surgery are eligible).
* Patients who have previously been diagnosed and treated for earlier stage ovarian, fallopian tube or primary peritoneal cancer.
* Patients who have previously received chemotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease).
* Patients with synchronous primary endometrial cancer unless both of the following criteria are met: 1) stage \<2 2) less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
B: Inclusion Criteria:

1. Age ≥ 18 years
2. Performance status ECOG \< 2
3. Histological documented ovarian, tubal or peritoneum carcinoma (stage IC to IV)
4. Patient treated at least with one line of platinum-based chemotherapy who have relapsed within 6 months after trhe last administration of platinum-based chemotherapy and taking bevacizumab for maintenance NB: Penultimate line of chemotherapy could contain chemotherapy without platinum and the last line should contain platinum-based chemotherapy (followed by bevacizumab for maintenance)
5. Patients must have disease that is measurable and/or evaluable according to RECIST criteria and requires chemotherapy treatment
6. Patients with liver metastasis can be included
7. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.
8. Life expectancy of more than 3 months
9. Able to swallow and retain oral medication
10. Adequate organ system function like:

Total bilirubin ≤ 1.5 X ULN Alanine amino transferase (ALT) and Aspartate aminotransferase (AST)c ≤ 2.5 X ULN

1. Subjects may not have had a transfusion within 7 days of screening assessment.
2. Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.
3. Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted.
4. If UPC \<1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value \<1 g to be eligible. Use of urine dipstick for renal function assessment is not acceptable. 10. Women of childbearing potential must agree to use effective contraception 11. Negative serum pregnancy test (if applicable) 12. Affiliated to or a beneficiary of a social security category

Exclusion Criteria:

1. Prior malignancy over the past 5 years with the exception of in situ carcinomas of the cervix or basal and squamous cell carcinoma or nonmelanoma skin cancer properly treated, or all solid tumor, considered as in completed remission without relapse for at least 5 years
2. Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants of P3A4 cytochrom
3. Previous treatment with monotherapy weekly paclitaxel
4. Previous treatment with bevacizumab within three weeks before start of studt treatment
5. Patients with severe hypersensitivity to a product containing castor oil polyoxyl 35 or paclitaxel solvent: the Chremophor
6. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

   * Active peptic ulcer disease
   * Known intraluminal metastatic lesion/s with risk of bleeding
   * Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other gastrointestinal conditions with increased risk of perforation
   * History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
7. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

   * Malabsorption syndrome
   * Major resection of the stomach or small bowel.
8. Corrected QT interval (QTc) \> 450 msecs or \> 480 msecs for patient with block branch
9. History of any one or more of the following cardiovascular conditions within the past 6 months:

   * Cardiac angioplasty or stenting
   * Myocardial infarction
   * Unstable angina
   * Coronary artery bypass graft surgery
   * Symptomatic peripheral vascular disease
   * Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
   * Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg\].
10. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
11. Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
12. to 14: All risk of bleeding

15 Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. 16 Unable or unwilling to discontinue use of prohibited medications 17 Treatment with any of the following anti-cancer therapies:

* radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib (out of bevacizumab) OR
* chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib (out of bevacizumab) 18 Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment 19 Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity, except alopecia. 20 Patient deprived of liberty or state-controlled 21 Inability to participate to medical follow up for geographic
C: Inclusion Criteria:

* Patient must have epithelial ovarian, fallopian tube, or primary peritoneal cancer
* Patients must have received ≥2 and not more than 5 prior therapies, including at least 1 line of therapy containing bevacizumab (or biosimilar).
* Patients must be considered platinum-resistant, defined as progression within 6 months from completion of a platinum-containing therapy
* Patient must be considered appropriate for treatment with weekly paclitaxel monotherapy as the next line of therapy.
* Patient must be willing and able to provide an FFPE archival or core tumor sample for determination of biomarker status on the Xerna™ TME Panel biomarker assay (positive or negative) prior to study treatment.
* Presence of at least one measurable lesion, as defined by RECIST v1.1.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 Adequate organ function

Exclusion Criteria:

* Non-epithelial ovarian carcinoma.
* Ovarian tumors with low malignant potential (i.e., borderline tumors).
* Primary platinum-refractory disease (defined as progression during or within 4 weeks after completion of the first platinum regimen).
* Patient has received an anti-angiogenic product other than bevacizumab or biosimilar.
* Patient has congestive heart failure
* Patient has a history of myocardial infarction, cerebral vascular accident, or transient ischemic attacks within 6 months
* Patient has a history of cardiac ischemia or heart failure within 6 months
* Baseline B-type natriuretic peptide (BNP) value \>100 pg/mL or N-terminal-proBNP (NT-proBNP) value of \> 125 pg/mL.
* LVEF \<50%.
* Peak tricuspid velocity \>3.0 m/s on Doppler ECHO.
* Clinically significant ECG abnormality, as assessed by the investigator
* Blood pressure (BP) \>140/90 mmHg
* History of bowel obstruction, including sub-occlusive disease, related to the underlying disease
* Hemoptysis \>2.5 mL within 8 weeks prior
* Major surgical procedure, or significant traumatic injury within 28 days
* Uncontrolled seizure disorder or active neurologic disease
* Patients with a cardiac aneurysm.
D: Inclusion Criteria:

* Diagnosed with serous ovarian cancer
* Patients who have received no more than 3 previous platinum containing treatments and were progression free for at least 6 months following the end of the last platinum treatment
* At least one lesion that is suitable for accurate repeated measurements

Exclusion Criteria:

* Patients receiving any systemic anticancer chemotherapy, radiotherapy (except palliative) within two weeks from the last dose prior to study treatment
* Hypersensitivity to pre medications required for treatment with paclitaxel/carboplatin

Answer: B