Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Randomized Phase II Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo in Ovarian Epithelial Cancer or Primary Peritoneal Cancer Patients Who Have Achieved a Complete Clinical Response After Standard Platinum/Taxane Containing Chemotherapy
Brief Summary: Comparison of Nexavar with a placebo as maintenance therapy for patients with advanced Ovarian or primary Peritoneal cancers in complete remission following surgery and one regimen of chemotherapy.


Options:
A: 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
B: Inclusion Criteria:

* Patients must have platinum-resistant/refractory (i.e., platinum-free interval \<6 months) recurrent or persistent histologically confirmed epithelial (non-mucinous) ovarian, fallopian tube, or primary peritoneal cancer.

Patients may have serous, endometrioid, clear cell, carcinosarcoma, or transitional cell/malignant Brenner, mixed, or undifferentiated histologies.

* Patients must have specimen available for immunohistochemistry for class III β-tubulin status; recurrent tumor specimen is preferred, though this may be performed on primary tumor if no recurrent tumor is available.
* All patients must have measurable disease. Measurable disease is defined as lesions that can be measured by physical examination or by means of medical imaging techniques. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation or plain x-ray, or ≥ 10 mm when measured by spiral CT and/or MRI. Ascites and pleural effusions are not to be considered measurable disease.
* Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST v1.1 Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
* At the time of initial surgery, patients may have been optimally (\<1 cm diameter residual disease) or sub-optimally (≥1 cm diameter of residual disease) debulked.
* Patients with measurable recurrent disease of any previous stage (I-IV) are eligible to enrollment.
* The diagnosis must be histologically confirmed by a gynecologic pathologist.
* Patients must have adequate bone marrow, kidney, and liver function:

  1. Absolute neutrophil count greater than or equal to 1500 cells/mm3
  2. Platelets greater than or equal to 100,000/uL
  3. Renal function: creatinine less than or equal to 2.0 mg/dL
  4. Hepatic function: Bilirubin ≤ 1.5 X laboratory normal
  5. SGOT/SGPT ≤ 3 X laboratory normal.
* Patients must have an ECOG performance status of 0-2.
* Patients must have signed an approved informed consent.
* Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy. They should be free of significant infection.
* Patients must have received prior treatment with taxanes. There is no limit on the number of prior lines of therapy.
* Patients may have received prior bevacizumab therapy alone or in combination with chemotherapy. A 3-week washout period is required.
* Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the study entry and be practicing an effective form of contraception (section 7.5.3).
* Patients must be at least 18 years of age.

Exclusion Criteria:

* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers, are excluded if there is any evidence of other malignancy present within the last five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
* Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, or uncontrolled arrhythmias within 6 months of registration (NYHA classification III-IV).
* Patients with any unstable medical issue (including cardiac issues as above, active treatment for symptomatic pulmonary embolism, CVA, renal or hepatic insufficiency, active infection/sepsis requiring intravenous antibiotics). In patients who have undergone surgery, 28 days should elapse before initiation and the surgical site should be adequately healed.
* Known brain/leptomeningeal involvement of the disease, active neurological disease such as uncontrolled seizure disorder or moderate to severe dementia.
* Patients who have received prior therapy with any covalent irreversible anti-angiogenic tyrosine kinase inhibitor (e.g., vandetanib).
* Patients known to be seropositive for human immunodeficiency virus (HIV) and active hepatitis, even if liver function studies are in the eligible range.
* Known hemorrhagic diathesis or active bleeding disorder, including platelet count \<100,000/uL, or inadequate granulocytes, including an absolute neutrophil count \<1500 cells/mm.
* Any hypersensitivity to Cremophor® EL or polyoxyethylated castor oil.
* CTCAE grade 2 or higher peripheral neuropathy.
C: Key Inclusion Criteria:

Female patients with newly diagnosed, histologically confirmed, advanced (Stage III-IV) high grade epithelial ovarian cancer including high grade serious, high grade endometriod, clear cell ovarian cancer or carcinosarcoma, primary peritoneal cancer and / or fallopian-tube cancer

* Patients must be aged ≥18 years of age. For patients enrolled in Japan that are aged \<20 year
* All patients should be candidates for cytoreductive surgery either: upfront primary surgery OR plan to undergo chemotherapy with interval debulking surgery
* Evidence of presence or absence of BRCA1/2 mutation in tumour tissue
* Mandatory provision of tumour sample for centralised tBRCA testing
* ECOG performance status 0-1
* Patients must have preserved organ and bone marrow function
* Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test

Key Exclusion Criteria:

Non-epithelial ovarian cancer, borderline tumors, low grade epithelial tumors or mucinous histology

* Prior systemic anti-cancer therapy for ovarian cancer
* Inability to determine the presence or absence of a deleterious or suspected deleterious BRCA mutation
* Prior treatment with PARP inhibitor or immune mediated therapy
* Planned intraperitoneal cytotoxic chemotherapy
* Active or prior documented autoimmune or inflammatory disorders
* Patients considered a poor medical risk due to a serious, uncontrolled intercurrent illness
* Clinically significant cardiovascular disease
* Patients with known brain metastases
* History of another primary malignancy except for:

  * Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study treatment and of low potential risk for recurrence (patients who have received prior adjuvant chemotherapy for early stage breast cancer may be eligible, provided that it was completed ≥3 years prior to registration, and that the patient remains free of recurrent or metastatic disease)
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  * Adequately treated carcinoma in situ without evidence of disease
  * Endometrial cancer FIGO Stage IA, Grade 1 or Grade 2
* Persistent toxicities CTCAE Grade \>2 caused by previous cancer therapy
* Patients with a known hypersensitivity to olaparib, durvalumab or any of the excipients of these products and to the combination/comparator agents
* Breast feeding women
D: Inclusion Criteria:

* Histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage (67) III or IV ovarian epithelial cancer or primary peritoneal cancer at presentation. Patients must have achieved a clinical complete response (disappearance of all clinical and radiological evidence of tumor) after only one regimen (4-6 cycles) of platinum and taxane-based standard chemotherapy received after tumor debulkment.
* Normal serum CA125 (cancer-associated tumor marker) level within 7 days of first dose of sorafenib.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* All scans used to document complete response must be done within 30 days prior to randomization.
* Patients must be able to swallow and retain oral medication.

Exclusion Criteria:

* Patients with any residual cancer tissue after the completion of chemotherapy detectable by standard Computed tomography (CT) or magnetic resonance imaging (MRI).
* Prior local radiotherapy, neoadjuvant chemotherapy or intraperitoneal chemotherapy.
* Histologic subtypes of ovarian cancer other than epithelial (i.e. sarcoma, lymphoma, germ cell).
* Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization.

Answer: D