Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Phase II Trial of Olaparib, Chemotherapy or Olaparib and Cediranib in Patients With Platinum-resistant Ovarian Cancer
Brief Summary: The trial will compare the drugs olaparib and cediranib with standard chemotherapy in platinum resistant ovarian cancer. Patients will be randomised to one of three treatment groups: olaparib only, olaparib and cediranib and the control group paclitaxel. The aim is to compare efficacy of the 3 treatments and also how well each treatment is tolerated including the participants quality of life.


Options:
A: Inclusion Criteria:

* Must be at least 18 years old
* Must have measurable or detectable ovarian, fallopian or primary peritoneal cancer
* Must have been treated previously with carboplatin, cisplatin or another organoplatinum compound

Exclusion Criteria:

* Women who are pregnant or nursing
* History of congenital long QT syndrome
* Active bleeding or at risk of a bleeding disorder
* Other significant medical condition or history of medical condition which may put the patient at risk
B: Inclusion Criteria:

* The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below:

  * Pancreatic Cancer
  * Castration-Resistant Prostate Cancer (CRPC)
  * Hepatocellular Carcinoma (HCC)
  * Gastric or Gastroesophageal Junction Cancer
  * Melanoma
  * Small Cell Lung Cancer (SCLC)
  * Ovarian cancer, primary peritoneal or fallopian tube carcinoma
  * Breast cancer that is one of the following subtypes: estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative), or inflammatory (regardless of receptor status) disease histology
  * Non-Small Cell Lung Cancer (NSCLC)
* Certain requirements for prior therapies may apply
* The subject has documented progressive disease at screening
* Subjects having any tumor type of other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan
* The subject has recovered to baseline or CTCAE ≤ Grade 1 from toxicities related to prior treatment (some exceptions apply)
* The subject is ≥ 18 years old on the day of consent
* Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor
* The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* The subject has adequate organ function
* The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
* Sexually active fertile subjects (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug(s)
* Female subjects of childbearing potential must have a negative pregnancy test at screening

Exclusion Criteria:

* The subject has experienced clinically-significant hematemesis or hemoptysis of \>0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
* The subject has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel
* Certain restrictions on prior treatments apply
* The subject has known symptomatic or uncontrolled brain metastases or epidural disease
* The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3x)the laboratory upper limit of normal
* The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (low-dose aspirin (≤81 mg/day), low-dose warfarin (≤1mg/day, and prophylactic low molecular weight heparin (LMWH) are permitted)
* The subject has a corrected QT interval(QTcF)\>500 ms at screening
* The subject has uncontrolled, significant intercurrent illness
* The subject is unable to swallow capsules
* The subject is pregnant or breastfeeding
* The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation
* The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
* The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer
C: Inclusion Criteria:

1. Female patients, age ≥ 16 years with relapsed epithelial ovarian, primary peritoneal or fallopian tube cancer who have relapsed within 12 months of previous platinum-based therapy. Their most recent chemotherapy does not have to have been platinum-based.
2. Patients can have received prior PARP inhibitor, but there must be a \> 6 month interval since treatment.
3. Patients can have received prior antiangiogenic therapy, but there must be a \> 6 month interval since treatment; except for bevacizumab where a 6 week interval is required.
4. Measurable disease by RECIST Version 1.1 performed in past 4 weeks. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
5. Sufficient archival tissue confirming histological diagnosis available.
6. ECOG PS 0-2
7. Able to swallow and retain oral medications.
8. Life expectancy \> 12 weeks in terms of disease related mortality
9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
10. Written (signed and dated) informed consent prior to any study specific procedures and be capable of co-operating with protocol.
11. Patients must have

    • Haemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to randomisation
12. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below:

    * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    * Platelet count \> 100 x 109/L
    * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    * AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
    * Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or calculated creatinine clearance \>50 ml/min calculated using Cockroft-Gault, Jelliffe or Wright (see Appendix 4)
    * 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.

Exclusion Criteria:

1. Received previous single agent weekly paclitaxel for relapsed disease.
2. Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used during the trial and for 6 months after stopping treatment. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. Pregnancy test will be performed monthly in women of child bearing potential.

   Postmenopausal is defined as:
   * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
   * LH and 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, or surgical sterilisation (bilateral oophorectomy or hysterectomy).
3. Treatment with any other investigational agent, systemic chemotherapy, or participation in another interventional clinical trial within 28 days prior to enrolment.
4. Radiotherapy within 2 weeks from the last dose prior to study treatment
5. Started a stable dose of bisphosphonates for bone metastases less than 4 weeks prior to treatment with study drug e.g. patient is eligible and can continue to take bisphosphonates if these were started at least 4 weeks prior to treatment with study drug.
6. Concomitant use of known CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
7. Concomitant use of potent inducers of CYP3A4 such as rifampicin, carbamazepine, phenobarbital, phenytoin and St. John Wort.
8. Persistent toxicities (\>=CTCAE grade 2) caused by previous cancer therapy with the exception of alopecia.
9. Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
10. Blood transfusions within 1 month prior to study start
11. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
12. Patients with symptomatic, untreated, uncontrolled brain or meningeal metastases or tumour.

    a. A scan to confirm the absence of brain metastases is not required. b. Patients with radiological evidence of stable brain metastases are eligible, providing that they are asymptomatic and: i. Do not require corticosteroids, or ii. Have previously been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids iii. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
13. Major surgery within 14 days of starting study treatment
14. Patients who have not recovered from any effects of any major surgery.
15. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan
16. Any psychiatric disorder that prohibits obtaining informed consent.
17. Left Ventricular Ejection Fraction (LVEF) \< institutional lower limit of normal, when:

    i. Prior treatment with anthracyclines (excluding liposomal doxorubicin) ii. Prior treatment with trastuzumab iii. A NYHA classification of II controlled with treatment (see Appendix 2) iv. Prior central thoracic RT, including RT to the heart v. History of myocardial infarction within the prior 12 months
18. Poorly controlled hypertension (persistently elevated \> 150/100mmHg, either systolic or diastolic or both, despite anti-hypertensive medication)
19. History of inflammatory bowel disease
20. History of cerebrovascular accident (including transient ischaemic attacks) within last 12 months.
21. Gastro intestinal impairment that could affect ability to take, or absorption of, oral medicines including sub- acute or complete bowel obstruction
22. Evidence of severe or uncontrolled cardiac disease
23. Evidence of active bleeding or bleeding diathesis. Defined as significant haemorrhage (\>30mL bleeding/episode in previous 3 months) or haemoptysis (\>5mL fresh blood in previous 4 weeks)
24. Known treatment-limiting hypersensitivity to cediranib, olaparib, paclitaxel or any of its excipients
25. Other psychological, 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.
26. Any other active malignancy, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions, requiring treatment/or whose prognosis will prevent readout from trial endpoints.
27. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.

28 Immunocompromised patients e.g., patients who are taking immunosuppressive drugs.
D: Inclusion Criteria:

* Histologically confirmed and documented high-risk FIGO stage IIIC/IV epithelial ovarian carcinoma, fallopian tube carcinoma, or primary peritoneal carcinoma
* Not eligible for primary complete debulking surgery during a laparoscopic procedure as judged by a surgeon experienced in management of ovarian cancer
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Life expectancy greater than or equal to (\>/=) 3 months
* Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards
* Beneficiaries of healthcare coverage under the social security system

Exclusion Criteria:

* Non-epithelial ovarian cancer, ovarian tumor with low malignant potential, mucinous and clear cell ovarian cancer, or carcinosarcoma
* Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
* Previous systemic therapy for ovarian cancer
* Previous exposure to mouse CA-125 antibody
* Current or recent (within 28 days prior to Day 1 of Cycle 1) treatment with another investigational drug or previous participation in this study
* Current or recent (within 10 days prior to first study drug dose) chronic daily treatment with aspirin greater than (\>) 325 milligrams (mg) per day
* Planned intraperitoneal cytotoxic chemotherapy
* Inadequate bone marrow, liver, or renal function
* History of myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to Day 1 of Cycle 1
* Uncontrolled hypertension
* Clinically significant (active) cardiovascular disease such as New York Heart Association (NYHA) Class II or greater congestive heart failure, or aortic aneurism
* Pre-existing peripheral neuropathy that is Common Toxicity Criteria (CTC) Grade \>/=2
* Known hypersensitivity to bevacizumab or its excipients, Chinese hamster ovary cell products or other recombinant humanized antibodies, or to any planned chemotherapy
* Pregnant or lactating females
* History of other clinically active malignancy within 5 years of enrollment, except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal-cell or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix or breast

Answer: C