Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Trial Of Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced Renal Cell Carcinoma Who Have Failed First-Line Sunitinib Therapy
Brief Summary: This is an international, randomized, open-label, outpatient, multicenter study. Subjects will be assigned in a 1:1 ratio to 1 of 2 treatment arms: temsirolimus 25 mg once weekly by intravenous (IV) infusion or sorafenib 400 mg by mouth (PO) twice daily (BID). These investigational drugs will be administered in 6-week cycles for the duration of the study, up to 24 months. Subjects will be stratified by nephrectomy status, duration of response to sunitinib therapy, Memorial Sloan Kettering Cancer Center (MSKCC) prognostic group, and RCC tumor histology.


Options:
A: 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.
B: Inclusion Criteria:

* Histologic confirmation of Renal cell carcinoma (RCC) with a clear cell component
* Previous treatment with at least one anti-angiogenic agent
* Progressed within 6 months of study enrollment
* Subjects should not have had more than 3 prior treatments for locally advanced or metastatic disease
* Must have available tumor tissue for submission
* Subjects must also meet various laboratory parameters for inclusion

Exclusion Criteria:

* Subjects with any active autoimmune disease or a history of known autoimmune disease

Other protocol-defined inclusion/exclusion criteria apply
C: 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
D: Inclusion Criteria:

* Histologically confirmed diagnosis of mRCC (regardless of histology or nephrectomy status) with well-documented Radiological PD by RECIST criteria or clinical PD as judged by the investigator while receiving first-line sunitinib therapy. Subjects must have at least 1 cycle of sunitinib therapy (minimum of four weeks continuously).
* At time of randomization, at least 2 weeks since prior treatment with sunitinib, palliative radiation therapy, and/or surgery.
* At time of randomization, there must be at least 1 measurable lesion per RECIST. Lesions that have been previously irradiated or embolized cannot be selected as target lesions.

  * More criteria apply

Exclusion Criteria:

* Metastatic CNS from RCC.
* Subjects who discontinued Sutent therapy due specifically to intolerance.
* Prior systemic therapy for mRCC other than sunitinib.
* Active ketonuria, secondary to poorly controlled diabetes mellitus

  * More criteria apply

Answer: D