Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Randomised, Double-blind, Parallel Group Study to Assess the Efficacy of Cediranib 45mg Versus Placebo Following 12 Weeks of Treatment in Patients With Metastatic or Recurrent Renal Cell Carcinoma Who Have Had no Previous Anti-VEGF Therapy.
Brief Summary: Cediranib is being tested to assess its effectiveness on the growth of kidney cancer tumours and also how well it is tolerated.


Options:
A: Inclusion Criteria:

1. Patients with metastatic / advanced RCC (all histologies), who are not suitable for cytokine therapy and for whom study medication constitutes first-line treatment. For cytokine- unsuitability at least one of the following criteria must be fulfilled\*:

   * Age 66 to 88 years
   * Non-clear cell histology RCC
   * Intermediate risk according to MSKCC score
   * ECOG ≥ 1 and\> 1 organ metastasis + \< 24 months between diagnosis and establishing indication for interleukin-2-therapy
   * ECOG ≥ 1 and "unable to carry on normal activity or do active work" (Karnofsky Index 70%)
   * Creatinine ≥ 1x ULN and \< 2x ULN
   * Total bilirubin ≥ 1x ULN and \< 1.5x ULN
   * Present autoimmune disease
   * Patients who might require steroids
   * Hypersensitivity against cytokines
   * Severe organic disease, not interfering with other in-/exclusion criteria of the Switch-2 study
   * Non-symptomatic brain metastases
   * Severe lung disease (e.g. PAH, COPD) with Pa O2 \< 60 mmHg on rest
2. Age ≥ 18 and ≤ 85 years
3. Karnofsky Index ≥ 70% (see appendix 15.1)
4. MSKCC prognostic score (2004), low or intermediate (see appendix 15.2)
5. Life expectancy of at least 12 weeks
6. Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by CT/MRI- scan
7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to start of therapy:

   * hemoglobin \> 9.0 g/dl
   * absolute neutrophil count (ANC) \> 1,500 µl
   * Platelet count ≥ 100,000 / µl
   * total bilirubin \< 1.5x the upper limit of normal (Note: Subjects with Gilbert' Syndrome are eligible if their total bilirubin is \< 3.0 X ULN and direct bilirubin ≤ 35 %).
   * ALAT and ASAT \< 2.5x upper limit of normal (Note: concomitant elevations in bilirubin ans ASAT/ALAT above 1.0x upper limit of normal are not permitted).
   * Alkaline phosphatase \< 4x upper limit of normal
   * PT-INR/aPTT \< 1.2x upper limit of normal (Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that their INR is stable and within the recommended range for the desired level of anticoagulation and no prior evidence of underlying abnormality in these parameters exists).
   * Serum creatinine \< 2x upper limit of normal
8. Written Informed Consent

Exclusion Criteria:

1. History of cardiac disease: congestive heart failure \> NYHA class 2 or with LVEF at baseline echocardiography \< 50%, (echocardiography is optional); active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
2. Uncontrolled hypertension (defined as blood pressure ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic on medication).
3. History of HIV infection or chronic hepatitis B or C
4. 4. Active clinically serious infections (\> grade 2 NCI-CTC version 4.03)
5. Symptomatic metastatic brain or meningeal tumors (unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
6. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
7. Patients with evidence or history of bleeding diathesis
8. History of organ allograft
9. Major surgery within 4 weeks of start of study
10. Autologous bone marrow transplant or stem cell rescue within 4 months before study start.
11. Any significant condition that increases the risk for bleeding, including, but not limited to active peptic ulcer disease, inflammatory bowel disease, known intraluminal or endobronchial metastatic lesions and/or lesions infiltrating major pulmonary vessels with risk of bleeding, presence of non-healing wound or trauma within 4 weeks prior to first dose of investigational drug
12. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep vein 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)
13. Corrected QT Interval (QTc) \> 480 msecs
14. Untreated hypothyroidism
15. Patients undergoing renal dialysis
16. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis \& T1\] or any cancer curatively treated \> 3 years prior to study entry
17. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures (with a Pearl Index \< 1) during the course of the trial and 3 months after the completion of trial
18. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
19. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
20. Patients unable to swallow oral medications
21. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
22. Known allergy to Votrient or Nexavar (i.e. to active substance or one of the constituents)
23. Prior exposure to study drugs.
24. Investigational drug therapy within 4 weeks of study entry.
25. Use of biologic response modifiers, such as G-CSF and other hematopoietic growth factors, within 3 weeks of study entry
26. Radiotherapy within 3 weeks of start of study drug and planned radiotherapy during the study
27. Concomitant medication: Any condition at the discretion of the investigator that precludes compliance with concomitant therapy restrictions described below.
B: Select Inclusion Criteria:

1. Documented histological or cytological diagnosis of renal cell cancer with a clear-cell component.
2. Measurable disease as determined by the investigator.
3. Must have received at least one VEGFR-targeting TKI (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib).
4. Recovery from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
5. Adequate organ and marrow function.
6. Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment.
7. Female subjects of childbearing potential must not be pregnant at screening.

Select Exclusion Criteria:

1. Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus), or cabozantinib.
2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization.
3. Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before randomization.
4. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Systemic treatment with radionuclides within 6 weeks before randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization.
6. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors.
7. Chronic treatment with corticosteroids or other immunosuppressive agents.
8. Serious illness other than cancer.
9. Major surgery within 3 months before randomization. Complete wound healing from major surgery must have occurred 1 month before randomization and from minor surgery at least 10 days before randomization.
10. Pregnant or lactating females.
11. Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low grade tumors.
C: Inclusion Criteria:

* Confirmation of metastatic or recurrent renal cell carcinoma

Exclusion Criteria:

* Certain types of previous anti-cancer therapy for Renal Cell Carcinoma
* Patients with type I insulin-dependent diabetes or poorly-controlled type II insulin-independent diabetes
* Patients with a history of poorly controlled high blood pressure
D: Inclusion Criteria:

* Histologically or cytologically confirmed renal cell cancer with a component of clear cell subtype, with metastasis
* Evidence of measurable disease
* Must have failed one prior systemic first-line regimen for metastatic renal cell cancer

Exclusion Criteria:

* Prior treatment for metastatic renal cell cancer with more that one systemic first line therapy
* Major surgery less than 4 weeks or radiation less than 2 weeks of starting study drug

Answer: C