Inclusion Criteria:

- Histological or cytological proof of component (any percent) of clear cell RCC (renal
cell carcinoma).

- Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not
mandatory.

- Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors (TKIs).

- Measurable disease according to RECIST and obtained by imaging within 30 days prior
to registration for protocol therapy.

- Written informed consent and HIPAA authorization for release of personal health
information.

- Age > 18 years at the time of consent.

- Females of childbearing potential and males must be willing to use an effective
method of contraception (hormonal or barrier method of birth control; abstinence)
from the time consent is signed until 4 weeks after treatment discontinuation.

- Females of childbearing potential must have a negative pregnancy test within 7 days
prior to registration for protocol therapy.

Exclusion Criteria:

- No active brain metastases. Patients with neurological symptoms must undergo a head
CT scan or brain MRI to exclude brain metastasis within 30 days prior to registration
on protocol therapy. NOTE: A patient with prior brain metastasis are eligible if
they have completed their radiation treatment for brain metastasis ≥30 days prior to
registration for protocol therapy, are off steroids, and are asymptomatic.

- No other currently active malignancy.

- No treatment with any investigational agent within 14 days prior to registration for
protocol therapy. NOTE: If treated with investigational agent within 14 days prior
to registration, AE must be resolved back to baseline.

- Prior cancer treatment must be completed at least 14 days prior to registration for
protocol therapy and the patient must have recovered from the acute toxic effects of
the regimen. With the exception of Bevacizumab treatment, which must be completed 30
days prior to registration for protocol therapy.

- Prior radiation therapy to < 25% of the bone marrow [see bone marrow radiation chart
in the study procedure manual (SPM)] allowed if completed within 30 days prior to
registration for protocol therapy.

- Corrected QT interval (QTc) ≤ 450 msec at least 7 days prior to registration for
protocol therapy.

- No clinically significant infections as judged by the treating investigator.

- No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis.

- No collecting duct, medullary or sarcomatoid histology.

- No prior treatment with temsirolimus or everolimus in the phase II component of the
study. NOTE: Prior treatment with these agents is permitted in the phase I component
of the study.

- No use of full dose, therapeutic anti-coagulation with warfarin or related
anti-coagulants or unfractionated or low molecular weight heparins.

- No uncontrolled hypertension (BP >150/100mmHg despite full doses of 1
anti-hypertensive medication).

- No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) of
registration for protocol therapy.

- No grade 2 or greater peripheral neuropathy.