MLN0128 and MLN0128 + MLN1117 Compared With Everolimus in the Treatment of Adults With Advanced or Metastatic Clear-Cell Renal Cell Carcinoma

1. Male or female participants aged 18 years or older.

2. Histologically confirmed renal cell carcinoma (RCC) with a clear-cell component.

3. Evidence that the RCC is advanced or metastatic.

4. Radiologic evidence of PD (according to RECIST Version 1.1) either during or within 6 months after stopping their most recent systemic therapy for RCC before enrollment into this study.

5. At least 1, prior line of VEGF-targeted therapy, but not more than 4 total prior lines of systemic therapy. Exposure to more than 1 line of VEGF-targeted therapy is acceptable. Participants may also have received prior therapies with interferon, interleukin 2 (IL-2), anti-PD1 antibodies, cabozantinib or other experimental agents, but not prior therapy with any agent that targets phosphoinositide 3-kinase (PI3K), serine/ threonine-specific protein kinase (AKT), or mechanistic (or mammalian) target of rapamycin (mTOR).

6. Karnofsky Performance Status (KPS) greater than or equal to (\>=) 70%.

7. Life expectancy of \>=3 months.

8. Female participants who:

* Are postmenopausal for at least 1 year before the screening visit, OR

* Are surgically sterile, OR

* If they are of childbearing potential, agree to practice 1 highly effective method of contraception, and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labelling \[example, United States Prescribing Information (USPI), Summary of Product Characteristics (SmPC), etc;\]) after the last dose of study drug, OR

* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).

Male participants, even if surgically sterilized (that is, status postvasectomy), who:

* Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug (or longer, as mandated by local labelling \[example, USPI, SmPC, etc\]), OR

* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.).

* Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug.

9. Suitable venous access for the study-required blood sampling.

10. Screening clinical laboratory values:

* Absolute neutrophil count \>=2000 per microliter (/mcL) and platelet count \>=100,000/mcL;

* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to (\<=) 2.5\*the upper limit of normal (ULN);

* Total bilirubin \<=1.5\*ULN;

* Estimated creatinine clearance by Cockcroft-Gault \>=40 milliliter per minute (mL/min) / 1.73 square meter (m\^2);

* Glycosylated hemoglobin (HbA1c) less than (\<) 7.0%, fasting serum glucose \<=130 milligram per deciliter (mg/dL), and fasting triglycerides \<=300 mg/dL.

11. At least 14 days since the end of prior systemic VEGF-targeted treatment (that is, sunitinib, pazopanib, axitinib, or sorafenib), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity (except alopecia and hypothyroidism) either to Grade 0 or 1 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4.03) or to baseline.

12. At least 21 days since the last dose of bevacizumab, other antibody, or interferon.

13. Voluntary written consent given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

What this study is about