Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind Study to Evaluate the Efficacy and Safety of Avastin Plus Roferon Compared With Placebo Plus Roferon on Overall Survival and Tumor Assessment in Nephrectomised Patients With Metastatic Clear Cell Renal Cell Carcinoma
Brief Summary: This 2-arm study will evaluate the efficacy and safety of Avastin versus placebo in combination with Roferon as first-line treatment in participants with metastatic renal cell cancer (clear cell type) who have had nephrectomy. The anticipated time of study treatment is 1-2 years, and the target sample size is greater than (\>)500 individuals.


Options:
A: Inclusion Criteria:

* metastatic renal cell cancer (clear cell type);
* nephrectomy;
* absence of proteinuria.

Exclusion Criteria:

* prior systemic treatment for metastatic renal cell cancer;
* major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start;
* presence of brain metastases or spinal cord compression;
* ongoing need for full dose anticoagulants;
* uncontrolled hypertension;
* clinically significant cardiovascular disease.
B: Inclusion Criteria:

* Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
* Evaluable Memorial Sloan Kettering Cancer Center risk score
* Measurable disease, as defined by RECIST v1.1
* Karnofsky performance status greater than or equal to 70%
* Adequate hematologic and end-organ function prior to randomization

Exclusion Criteria:

Disease-Specific Exclusions:

* Radiotherapy for RCC within 14 days prior to treatment
* Active central nervous system disease
* Uncontrolled pleural effusion, pericardial effusion, or ascites
* Uncontrolled hypercalcemia
* Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death

General Medical Exclusions:

* Life expectancy less than 12 weeks
* Participation in another experimental drug study within 4 weeks prior to treatment
* Pregnant or lactating women
* Known hypersensitivity to any component of atezolizumab or other study medication
* History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
* Positive human immunodeficiency virus test
* Active or chronic hepatitis B or C
* Severe infections within 4 weeks prior to treatment
* Exposure to oral or IV antibiotics within 2 weeks prior to treatment
* Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
* Significant cardiovascular disease
* Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria Related to Medications:

* Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
* Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment

Bevacizumab- and Sunitinib-Specific Exclusions:

* History of hypertensive crisis or hypertensive encephalopathy
* Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds
C: 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 therapy
2. Age \>= 18 ans \<= 85years
3. ECOG Performance Status of 0 or 1
4. MSKCC prognostic score, low or intermediate
5. Life expectancy of at least 12 weeks.
6. Subjects with at least one uni-dimensional (for RECIST) 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/mm³
   * Platelet count \>= 100,000/μl
   * Total bilirubin \<= 1.5 times the upper limit of normal
   * ALT and AST \<= 2.5 x upper limit of normal (\<= 5 x upper limit of normal for patients with liver involvement of their cancer)
   * Alkaline phosphatase \< 4 x upper limit of normal
   * PT-INR/PT \< 1.5 x upper limit of normal \[Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.\]
   * Serum creatinine \<= 2 x 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%; 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) or uncontrolled hypertension (defined as blood pressure \>= 160 mmHg systolic and/or \>= 90 mmHG diastolic on medication).
2. History of HIV infection or chronic hepatitis B or C
3. Active clinically serious infections (\> grade 2 NCI-CTC version 3.0)
4. 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)
5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
6. History of organ allograft
7. Patients with evidence or history of bleeding diathesis
8. untreated hypothyrosis
9. Patients undergoing renal dialysis
10. 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.
11. 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 during the course of the trial and 3 months after the completion of trial.
12. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
13. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
14. Patients unable to swallow oral medications
15. Known allergy to sunitinib or sorafenib or one of its constituents

Excluded therapies and medications, previous and concomitant:

1. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
2. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study
3. Autologous bone marrow transplant or stem cell rescue within 4 months of study
4. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.

   \[G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.\] \[Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study\]
5. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
6. Prior exposure to the study drug.
7. Any St. John's wort containing remedy
D: 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.

Answer: A