Sorafenib Tosylate and Hypoxia-Activated Prodrug TH-302 in Treating Patients With Advanced Kidney Cancer or Liver Cancer That Cannot Be Removed By Surgery

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.

* Pregnant women

* Nursing women

* Men or women of childbearing potential who are unwilling to employ adequate contraception for the duration of study participation. Men and women should continue to use adequate birth control after the last administration of sorafenib and TH-302 under the guidance of their treating physician.

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

Receiving any other investigational agent.

Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer.

Inadequately controlled hypertension (systolic blood pressure of \>150 mmHg or diastolic pressure \>100 mmHg on anti-hypertensive medications).

Major surgical procedures, or significant traumatic injury ≤14 days prior to registration or anticipation of need for elective or planned major surgical procedure during the course of the study.

New York Heart Association (NYHA) classification III or IV congestive heart failure.

Received treatment with radiation therapy or investigational therapy ≤28 days prior to registration.

RCC patients only: Having received chemotherapy prior to study entry within 5 half-lives of the agent (as described in the package insert), or 4 weeks prior to registration (whichever is shorter) with resolution of side effects from therapy to ≤grade 1.

Known central nervous system or brain metastasis that are either symptomatic or untreated. Note: Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.

* Note: Subjects with CNS metastases that have been treated and are stable without symptoms for ≥ 4 weeks after completion of treatment are eligible.

HCC patients only: Cancer potentially amenable to local modalities of therapy or surgical resection.

Known or suspected allergy or hypersensitivity to any component of TH-302, sorafenib, or any of the sorafenib excipients.

Any condition that severely impairs patient's ability to swallow whole pills.

QTc interval \>500 msec on baseline EKG.

Documented history of prolonged QTc interval ≤ 6 months prior to registration.

Receiving any medication that has documented data or is generally accepted as having increased risk of QT prolongation and/or Torsades de Pointes.

Receiving any medications or substances that are inducers or strong or moderate inhibitors of CYP3A4, see the protocol for a complete listing.

Fibrolamellar histology HCC, mixed hepatocholangiocarcinoma, hepatic sarcomas and other non-HCC primary liver tumors.

History of lobectomy involving \>50% of lobe.

Radioembolization within 8 weeks of Day 1 dosing of sorafenib.