Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Open-Label, Comparative Bridging Study of CAELYX® Versus Topotecan HCl in Subjects With Epithelial Ovarian Carcinoma Following Failure of First-Line, Platinum-Based Chemotherapy
Brief Summary: The purpose of this study is to compare the effectiveness between CAELYX and topotecan hydrochloride (HCl) in Chinese participants with recurrent epithelial ovarian carcinoma following failure of first-line, platinum-based chemotherapy, who have received no more than one prior platinum-based regimen therapy.


Options:
A: Inclusion Criteria:

* Histopathologically documented invasive epithelial ovarian carcinoma, cancer of the fallopian tube or the peritoneum refractory to platinum-based chemotherapy or with partially platinum sensitive disease.
* Planned therapy with pegylated liposomal doxorubicin 50 mg/m² for recurrent platinum-refractory ovarian cancer.
* Patients with a progression-free-interval of 6 to 12 months after platinum-based chemotherapy are only eligible if a further course of platinum-based combination chemotherapy is not possible as judged by the investigator(s).
* Patients must have received at least one previous platinum- and taxane-based chemotherapy regimen.

Exclusion Criteria:

* Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days
* Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes or induce CYP3A4 function
* Treatment with mouse-antibodies in patients with evaluable disease and CA-125 progressive disease in the last 3 months. These patients are only eligible in case of measurable disease according to RECIST or cytological/histological proven relapse
* More than two prior lines of chemotherapy.
* Any chemotherapy or other systemic anti-cancer therapy within four weeks prior to randomization.
* Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy
B: Registration Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures and the ability to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.
2. Females aged ≥ 18 years with previous histologically proven diagnosis of high grade serous or endometrioid carcinoma of the

   * Ovary
   * Fallopian tube
   * or peritoneum, progressing \>6 months after day 1 of the last cycle of first-line platinum-based chemotherapy and requiring treatment with platinum-based chemotherapy on the basis of radiological evidence of disease or following surgical resection of recurrent disease.
3. Patients must have had CT or MRI proven relapsed disease (measureable or non-measureable abnormalities supported by GCIG CA125 criteria of progression), or have had debulking surgery for first relapse.
4. Patients showing evidence of response to chemotherapy mid-treatment (post 3 or 4 cycles), either by CA125 or CT/MRI scan, should be approached for ICON9 trial registration to allow for BRCA mutation status to be assessed (germline and/ or somatic). Patients who underwent surgical debulking must show no evidence of disease progression by the assessments above (CA125 and CT/MRI scan) in order to be approached for registration.
5. Prior front-line maintenance therapy with bevacizumab is permitted.
6. ECOG performance status 0-1.
7. Formalin fixed, paraffin embedded (FFPE) archival/diagnostic tumour sample or from secondary debulking surgery with adequate neoplastic cell content (\>30%), must be available for central BRCA testing. For inclusion in i) the genetic HRD Test and ii) the biomarker research, patients must complete the consent form. Translational blood samples are also required, see Laboratory Manual for further details.
8. Patients should have a life expectancy ≥ 16 weeks.
9. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days prior to study treatment and confirmed prior to treatment on day 1.

   Postmenopausal is defined as age ≥60 years, or:
   * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
   * Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
   * Radiation-induced oophorectomy with last menses \>1 year ago
   * Chemotherapy-induced menopause with \>1 year interval since last menses
   * Surgical sterilisation (bilateral oophorectomy or hysterectomy)
10. Adequately controlled blood pressure (systolic blood pressure \[SBP\] ≤140 mmHg; diastolic blood pressure \[DBP\] ≤ 90mmHg) on maximum of 2 antihypertensive medications.
11. Adequately controlled thyroid function, with no symptoms of thyroid dysfunction.

Randomisation Inclusion Criteria:

1. Patients must have received at least 4 cycles, and a maximum of 6 cycles of second-line platinum-based chemotherapy.
2. In patients with measurable disease, end of treatment scans must have a RECIST v1.1 'partial response' or 'complete response' and meet one of the following CA125 requirements:

   1. If the first screening CA125 value is below the ULN the patient is eligible for randomisation and a second CA125 assessment is not required.
   2. If the first screening CA125 value is greater than ULN then a second assessment is required at least 7 days after the first to confirm eligibility. If the second CA125 value has risen by ≥ 15% then the patient will not be eligible.
3. In patients with non-measurable disease, who have not undergone debulking surgery, they must have had a GCIG CA125 response to chemotherapy and meet one of the following CA125 requirements:

   1. If the first screening CA125 value is below the ULN the patient is eligible for randomisation and a second CA125 assessment is not required.
   2. If the first screening CA125 value is greater than ULN then a second assessment is required at least 7 days after the first to confirm eligibility. If the second CA125 value has risen by ≥ 15% then the patient will not be eligible.
4. Patients who have had debulking surgery at first relapse must have no evidence of disease progression on imaging (CT or MRI) and meet one of the following CA125 requirements:

   1. If the first screening CA125 value is below the ULN the patient is eligible for randomisation and a second CA125 assessment is not required.
   2. If the first screening CA125 value is greater than ULN then a second assessment is required at least 7 days after the first to confirm eligibility. If the second CA125 value has risen by ≥ 15% then the patient will not be eligible.
5. Expected to be able to commence treatment within 7 days post randomisation, and within 4-8 weeks post day 1 of the last cycle of chemotherapy.
6. Adequate bone marrow function as defined below:

   * Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/l
   * Platelet (Plt) ≥ 90 x 109/l
   * Haemoglobin (Hb) ≥ 100g/l required and no packed blood transfusions in the 14 days prior to starting trial treatment
7. Adequate liver function as defined below:

   * Serum bilirubin ≤ 1.5 x ULN (or ≤ 3 for cases of known Gilbert's syndrome)
   * Serum transaminases ≤3 x ULN
   * Serum transaminases ≤ 5 x ULN if liver metastasis present
8. Adequate renal function as defined below:

   • Serum creatinine ≤ 1.5 x ULN and calculated glomerular filtration rate (GFR) ≥50ml/min (calculated as per local practice using Wright or Cockroft-gault formula)
9. Urine dipstick for proteinuria \<2+. If urine dipstick is ≥ 2+ on two occasions more than one week apart then a 24-hour urine must demonstrate ≤ 1 g of protein in 24 hours or protein/creatinine ratio \< 1.5.
10. Adequately controlled blood pressure (systolic blood pressure \[SBP\] ≤140 mmHg; diastolic blood pressure \[DBP\] ≤ 90mmHg) on maximum of 2 antihypertensive medications.
11. Germline and/or somatic BRCA mutation status must be known prior to randomisation.

Exclusion Criteria:

1. Non-epithelial ovarian cancer, carcinosarcoma, clear cell carcinoma and mucinous carcinomas.
2. Arterial thrombotic event (including transient ischemic attack, cerebrovascular accident, and peripheral arterial embolus) within the last 12 months.
3. Patients unable to swallow orally administered medication and patients with gastrointestinal impairment that could affect ability to take, or absorption of oral medicines including sub-acute or complete bowel obstruction.
4. Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment.
5. History of intra-abdominal abscess within 3 months prior to starting treatment (randomisation).
6. History of GI perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula.
7. Symptomatic or clinically significant inflammatory bowel disease (Crohn's disease or ulcerative colitis).
8. Patients with an ileostomy will be excluded.
9. Evidence of severe or uncontrolled cardiac disease.

   1. Myocardial infarct or unstable angina within the last 6 months
   2. New York Health Association (NHYA) ≥ grade 2 congestive heart failure
   3. Cardiac ventricular arrhythmias requiring medication
   4. History of 2nd or 3rd degree atrioventricular conduction defects
10. Resting ECG with QTcF \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
11. Evidence of active bleeding or bleeding diathesis.

    Significant haemorrhage of \>30ml in a single episode within the last 3 months or any haemoptysis (\>5ml fresh blood in last 4 weeks).
12. Malignancy treated within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, Stage 1, grade 1 endometrial carcinoma.
13. Previous treatment with VEGFR tyrosine kinase inhibitors or PARP inhibitors are not permitted.
14. Patients with a known hypersensitivity to excipients of cediranib or olaparib.
15. Persisting ≥ grade 2 CTCAE toxicity (except alopecia and neuropathy) from previous anti-cancer treatment.
16. Major surgery within 14 days before anticipated start of treatment and patients must have recovered from any effects of major surgery.
17. Inability to attend or comply with treatment or follow-up scheduling.
18. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicated the use of an investigation drug or puts the patients at high risk for treatment-related complications.
19. Pregnant or breast-feeding women are excluded. Women of childbearing potential will be excluded unless effective methods of contraception are used from signing of the informed consent, throughout the period of taking study treatment and for at least 6 weeks after last dose of trial drug(s).
20. Treatment with any other investigational agent, or participation in another interventional clinical trial within 28 days prior to enrolment (randomisation).
21. Concomitant use of known strong CYP3A4 inhibitors (such as systemic ketoconazole, itraconazole, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir, telithromycin and clarithromycin or moderate CYP3A inhibitors (e.g. systemic Ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
22. Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
23. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
24. Other psychological, psychiatric, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.
25. Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
26. Immunocompromised patients e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
27. Patients with symptomatic uncontrolled brain or meningeal metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment.
28. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
29. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
C: Inclusion criteria:

* first diagnosis of histologically confirmed epithelial ovarian cancer, fallopian tube or primary peritoneal cancer
* International Federation of Gynecology and Obstetrics (FIGO) Stages IIB - IV
* females, age 18 years or older
* life expectancy of at least 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* prior surgery, defined as either (a) debulking surgery with maximum surgical effort at cytoreduction with the goal of no residual disease or (b) biopsy or limited surgery in patients with stage IV disease for whom surgical debulking was not considered appropriate, if diagnosis is confirmed by histology and no surgery is planned prior to disease progression (including interval debulking surgery)
* patient has given written informed consent which must be consistent with the International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local legislation
* planned application of first dose of chemotherapy after wound healing, but no later than 10 weeks after surgery

Exclusion criteria:

* histologic diagnosis of a benign or borderline tumour or of a malignant tumour of non-epithelial origin of the ovary, the fallopian tube or the peritoneum
* planned surgery within 124 weeks after randomisation in this trial, including interval debulking surgery
* clinically relevant non-healing wound, ulcer or bone fracture
* clinical symptoms or signs of gastrointestinal obstruction that require parenteral nutrition or hydration
* brain metastases
* pre-existing sensory or motor neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher, except due to trauma
* history of major thromboembolic event
* known inherited or acquired bleeding disorder
* significant cardiovascular diseases
* clinically relevant pericardial effusion
* history of a cerebral vascular accident, transient ischemic attack or subarachnoid haemorrhage within the past 6 months
* inadequate safety laboratory values
* serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal) or antiviral therapy, including Hepatitis B, Hepatitis C, Human Immunodeficiency Virus (HIV)
* poorly controlled diabetes mellitus or other contraindication to high dose corticosteroid therapy
* gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
* other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included if adequately treated: non-melanomatous skin cancer, cervical carcinoma in situ, carcinoma in situ of the breast, low risk endometrial cancer
* prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy)
* prior systemic cytotoxic chemotherapy
* prior treatment with BIBF 1120 or any other angiogenesis inhibitor
* prior radiotherapy
* serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease or a laboratory abnormality that may increase the risk associated with study participation or study drug administration
* Women of childbearing potential who are sexually active and not using a highly effective method of birth control during the trial and for at least twelve months after the 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
* patients unable to comply with the protocol
* any contraindications for therapy with paclitaxel or carboplatin
* 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
D: Inclusion Criteria:

* Histological diagnosed with epithelial ovarian carcinoma with measurable disease
* Recurrent epithelial ovarian carcinoma or disease progression following failure of first-line, platinum-based chemotherapy with no more than one prior platinum based regimen therapy
* Adequate laboratory values of bone marrow function, renal function, liver function, and echocardiogram tests
* Agrees to use protocol-defined effective contraception. A woman must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction
* Disease-free from prior malignancies for more than 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

Exclusion Criteria:

* Females who are pregnant or breast feeding or planning to become pregnant while enrolled in this study or within 1 year after the last dose of study medication
* Myocardial infarct within 6 months before enrollment, class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
* Uncontrolled systemic infection that requires systemic anti-infective treatment
* Prior therapy with CAELYX or topotecan HCl
* Prior chemotherapy within 28 days of first dose of study medication (or 42 days if participant has received a nitrosourea or mitomycin)

Answer: D