Have at least one evaluable and measurable lesion as defined by RECIST v.. Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or within the field and has shown ?% growth in size since post-treatment assessment. Underwent hepatic radiation, chemoembolization, and radiofrequency ablation < weeks prior to Day . Unsuitable for resection or transplant or radiofrequency ablation (RFA) NO hepatic artery embolization or cryoablation/radiofrequency ablation of hepatic metastasis within months of study treatment start Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible Patients must have disease that is not amenable to potentially curative resection or ablative techniques or that has recurred following ablative techniques. In addition, disease must not be amenable to transhepatic arterial chemoembolization (TACE) or must have progressed on TACE. Patients must not be candidates for liver transplantation. Patient who has received previous systemic therapy or transarterial chemoembolization (TACE) for HCC No other investigational, biologic or chemotherapy agents, localized ablation or chemoembolization for weeks prior to study entry Other locoregional therapy [e.g., radiofrequency ablation (RFA), TACE (transarterial chemoembolization), TARE (transarterial radioembolization), DEB-TACE (drug eluting bead transarterial chemoembolization)]: weeks Any liver directed treatment (surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation) within weeks prior to enrollment Prior embolization and/or ablation; for the dose escalation, prior embolization and ablation is allowed as long as the patient has progressed with a new RECIST measurable lesion No prior Y radioembolization for HCC is permitted; therapies below are allowed but must be completed weeks prior to baseline scan:\r\n* Prior transarterial embolization (TAE) or transarterial chemoembolization (TACE)\r\n* One treatment of stereotactic body radiation therapy (SBRT)\r\n* Liver resection\r\n* Ablation therapy Patients previously treated with any intra-arterial regional hepatic therapy such as trans-arterial chemoembolization. Prior surgery (not including TURP), cryosurgery, radiofrequency ablation, chemotherapy or radiation for PCa For patients who have received prior radiation, cryotherapy, radiofrequency ablation, TheraSphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:\r\n* days have elapsed since that therapy\r\n* Lesions that have not been treated with local therapy must be present and measureable Prior radiofrequency ablation (RFA) to index lesion COHORT B, GROUP : HEPATOCELLULAR CARCINOMA: Patients must have advanced disease that is not amenable for resection or transplantation, and that is not treatable with liver directed modalities such as radiofrequency ablation or transarterial chemoembolization Previous liver-directed treatments including chemoembolization, radiosphere, hepatic arterial perfusion, or drug-eluting beads Hepatic intra-arterial embolization or peptide receptor radionuclide therapy (PRRT) within - weeks; cryoablation, radiofrequency ablation or trans-arterial chemoembolization of hepatic metastases within ? weeks of study enrollment Receiving, or previously received, any systemic chemotherapy, or investigational agent for HCC\r\n* Note: prior surgical resection with recurrence, or palliative local therapy (including transcatheter arterial chemoembolization [TACE], Y- resin microspheres, etc.) would not exclude trial participation, but must have been performed at least months prior to enrollment Arterial anatomy which would preclude selective transarterial chemoembolization Patients must be candidate for surgical resection, ablation, and transarterial chemoembolization (TACE). Participants may have had prior chemotherapy, targeted biological therapy (i.e. sorafenib), surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occurred more than weeks before the first radiation treatment; patients may not have had prior liver directed radiation, including radioembolization Prior transarterial chemoembolization (TACE) or radiofrequency ablation (RFA) allowed, however, patient must have separate intrahepatic lesion amenable to SBRT and biopsy Is not a candidate for local therapies, including liver transplantation, tumor ablation, transarterial embolization, or resection Non-resectable, recurrent, or metastatic well- or moderately-differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within the last months; (patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of > % in the size; prior local therapy must be completed at least weeks prior to the baseline scan) Patients who received prior local therapy (e.g., transarterial chemoembolization [TACE]) are eligible Has received locoregional therapy to liver (transarterial chemoembolization (TACE), transarterial embolization (TAE), radiation, radioembolization, or ablation) or surgery to liver or other site within weeks prior to the first dose of study drug; minor surgery must have occurred at least days prior to the first dose of study treatment (cycle , day ); subjects must have recovered adequately (i.e., grade =< or baseline) from the toxicity and/or complications from any intervention prior to starting therapy Time interval for last local therapy (radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than weeks prior to registration Need or plans for concomitant antineoplastic therapy (including surgery, cryotherapy, radiofrequency ablation, chemo-embolization, conventionally fractionated radiotherapy, stereotactic body radiation therapy, and hepatic artery chemotherapy) for the protocol treated lesions except at progression; adjuvant systemic therapy before and after the protocol therapy, and surgery or other ablative therapy is allowed for lesions appearing after enrollment to this protocol is allowed; at least weeks must have passed since the last directed intervention to the protocol-treated lesion Patients must have multiple tumor lesions (at least ): one for the ablation procedure and another for evaluation located outside the proposal ablation zone Disease must be technically amenable to transhepatic arterial chemoembolization (TACE) (HCC patients only), radiofrequency ablation (RFA), or cryoablation; each case will be discussed at gastrointestinal (GI) tumor board with interventional radiology; patients must have evaluable disease For patients who have received prior radiation, cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:\r\n* days have elapsed since that therapy\r\n* Lesions that have not been treated with local therapy must be present and measurable Prior history of surgical resection, chemotherapy, transarterial chemoembolization (TACE), and/or radiofrequency ablation are allowed Any prior arterial liver-directed therapy, including transarterial chemoembolization (TACE), arterial embolization (TAE), and Y radioembolization Patients with oligometastatic NSCLC (defined as =< metastatic sites of disease), all treated with definitive intent using radiation, surgery, radiofrequency ablation (RFA), chemoradiation therapy, other definitive modalities or combinations of these Prior local therapy, such as surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment; local therapy must have been completed at least weeks prior to the baseline scan HCC not amenable to surgical resection, liver transplantation, chemoembolization, or ablation therapy Subject has received any treatment for the treating renal mass; such as radiofrequency ablation (RFA) or cryoablation\r\n* If other renal masses received RFA or cryoablation or surgery, then these patients are eligible Prior TACE Prior TACE, radiofrequency ablation (RFA), or liver transplant Previous systemic chemotherapy or non-radiation local therapy (such as surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) is allowed; the lesion must however have shown criteria of progression based on RECIST; local therapy must be completed at least weeks prior to the baseline scan; this is to create a safer treatment environment and to help determine the effect of treatment by SBRT alone; patients will be allowed to go onto appropriate systemic therapy, as determined by their medical oncologist, weeks following delivery of SBRT No liver surgery (including radiofrequency ablation), chemotherapy (including bevacizumab), immunotherapy, or liver radiotherapy within weeks of enrollment in this clinical trial Surgery: Subjects who have received hepatic surgery, ablation or chemoembolization within weeks of PV- administration. Patient who are receiving concurrent combination with sorafenib (Nexavar) and TACE (transarterial chemoembolization) in their originating study will be eligible. Concurrent anti-cancer chemotherapy, except TACE (transarterial chemoembolization), during or within days prior to start of study drug Any local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ? weeks before first dose of study medication. Note: patients who received sole intrahepatic intra-arterial chemotherapy, without lipiodol or embolizing agents are not eligible. HCC patients only: prior regional treatments for liver metastasis are permitted including:\r\n* Selective internal radiation therapy such as brachytherapy, cyber knife, radiolabeled microsphere embolization, etc.\r\n* Hepatic artery chemoembolization\r\n* Hepatic artery embolization\r\n* Hepatic artery infusional chemotherapy\r\n* Radiofrequency ablation\r\n* NOTE: patients must be >= weeks from treatment and show progressive measurable/evaluable disease in the liver after regional therapy or must have measurable disease outside the liver Prior chemotherapy, targeted biological therapy (e.g. sorafenib), surgery, transarterial chemoembolization (TACE), ablation for present disease is acceptable Cryoablation, radiofrequency ablation, or trans-arterial embolization of hepatic metastases ARM A: Any radioembolization or transarterial chemoembolization (TACE) =< days prior to registration Patients must have recovered from the acute effects of prior liver-directed therapy (e.g. RT, radiofrequency ablation [RFA], or transarterial chemoembolization [TACE]), and a minimum of weeks must have passed since the last procedure and protocol therapy Liver-directed therapy (chemoembolization, radioembolization, bland embolization, ablative therapy) within weeks of DEB-TACE Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within weeks prior to the first dose of study drug. Prior intra-arterial liver directed therapy, including transcatheter arterial chemoembolization (TACE) or Y- microsphere therapy Hepatic artery embolization or ablation of hepatic metastasis within months of enrollment, prior peptide receptor radionuclide therapy (PRRT) within months or any other cancer therapy within weeks (as long as all toxicities are resolved) Prior treatment with transarterial chemoembolization (TACE) or bland embolization > months prior to randomization and must have been applied to a treatment field and/or lobe not targeted for treatment under this protocol Patients that have been previously treated with chemotherapy for hepatoblastoma or other hepatoblastoma-directed therapy (eg, radiation therapy, biologic agents, local therapy [embolization, radiofrequency ablation, laser]) are not eligible Allowed prior therapies include:\r\n* Surgery (major surgery at least more than four weeks prior to baseline assessment)\r\n* Locoregional therapy such as: chemoembolization, radio-embolization, radiofrequency ablation, radiotherapy as long as there is progressive measurable disease outside the area of locoregional therapy or there is progression in the previously treated areas\r\n* Any number of previous lines of systemic therapy; last treatment before enrollment must have occurred more than weeks for chemotherapy, weeks for antibodies or more than half-lives of prior tyrosine kinase inhibitors (TKIs) or small molecules Subject's lesions are not amenable to local therapies which may be beneficial, such as transarterial chemoembolization (TACE), radiofrequency ablation, radiotherapy, etc., and the subject is not a candidate for any curative treatments such as resection or liver transplant. Subject had previous local therapy (e.g., surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within days prior to Day , has not recovered from toxicities from prior local therapy or may require major surgical procedure during the course of the study. For patients who have received prior cryotherapy, radiofrequency ablation, radioembolization, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, at least days must have elapsed since that therapy, and lesions that have not been treated with local therapy must be present and measurable. Prior cytotoxic therapy and immunotherapy are allowed; for the dose escalation, prior targeted therapy with a MEK inhibitor, protein kinase C inhibitor, Akt, or mTOR inhibitor are allowed; for the dose expansion cohort, no prior MEK, protein kinase C (PKC), Akt, or mTOR inhibitors are allowed, and registration is limited to total patients; local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least days prior to initiation of study therapy; lesions treated with local or regional modalities such as radiofrequency ablation, or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of months on subsequent imaging studies For patients who have received prior cryotherapy, radiofrequency ablation, Therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met: days have elapsed since that therapy (lesions that have not been treated with local therapy must be present and measurable) Patients may have been treated with locoregional therapies such as major surgery, radiation, radiofrequency ablation, or cryosurgery provided this has been completed at least weeks prior to registration and recovered from therapy related toxicity to less than CTCAE grade The target lesion(s) has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) Patients who have received local therapy, such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible if the previously treated lesions have progressed or recurred can be identified as target lesions; local therapy must have been completed at least weeks prior to the baseline scan Disease must be technically amenable to transhepatic arterial chemoembolization (TACE), radiofrequency ablation (RFA), or cryoablation; each case will be discussed at gastrointestinal (GI) tumor board with interventional radiology; patients must have evaluable disease Patients may have been treated with locoregional liver directed therapies such as embolization, chemo-embolization including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded), radiation, radioactive microspheres, etc., provided that they either have a target lesion that has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of >= % in the size since last treatment; such therapy must be completed at least weeks prior to treatment initiation; patients that have received palliative radiation therapy to the bone need not wait weeks to begin protocol therapy Prior loco-regional therapy including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded) is allowed Patients must have measurable disease per RECIST . criteria defined as at least one lesion that can be accurately measured in at least one dimension, and that has not been the target of local or regional therapy including transarterial chemoembolization, intra-arterial chemotherapy, ethanol or radiofrequency ablation Patients who have had any prior line of systemic therapy including cytotoxic agents or molecularly targeted agents for advanced/unresectable disease; any number of prior regional therapies with transarterial chemoembolization (TACE), brachytherapy with yttrium- microsphere, intra-arterial chemotherapy, surgery, or ablative therapy are allowed Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of >= % in the size; prior local therapy must be completed at least weeks prior to the baseline scan Patients with a prior history of liver directed therapy for their HCC (chemoembolization, radioembolization, bland embolization, radiation therapy, radiofrequency ablation, microwave ablation) can participate in the study if the liver-directed therapy was performed more than weeks prior to their first dose of sorafenib and measurable lesions present outside of previously treated field Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period. Local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >/= weeks before first dose of study medication. Note: patients who received sole intrahepatic intraarterial chemotherapy, without lipiodol or embolizing agents are not eligible. Patients who have received prior locoregional therapy for metastatic disease including surgical resection, microwave ablation, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, or radiation are eligible providing the measurable disease is clearly manifest and is outside of the radiation port or ablation field; patients who have received liver directed treatments such as yttrium- radioembolization or transarterial chemoembolization are eligible if their measurable disease is outside of the liver Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within weeks prior to randomization in the study. Prior transarterial chemoembolization (TACE) Any prior therapies such as surgery, chemoembolization, radiofrequency ablation, and alcohol injection are allowed as long as toxicity from such prior therapy is =< grade Previous surgery or radiofrequency ablation (RFA) to the liver is allowed; patients with history of chemoembolization or radio-labeled microspheres are excluded The study will be limited to patients who are chemotherapy naive; patients may have received prior systemic or liver-directed local therapies for advanced uveal melanoma as long as those treatments do not involve chemotherapy; this includes, but is not limited to: immunotherapy, targeted therapy, transarterial embolization, radiofrequency ablation, or cryoablation; treatment must be completed at least days prior to initiation of study therapy; radiation therapy is also allowed and must be completed at least days prior to initiation of study therapy; lesions treated via radiation or liver-directed therapy may not be used as target lesions unless they demonstrate growth over a minimum of months on subsequent imaging Measurable disease using RECIST . criteria (Appendix A). At least measurable lesion must be present. Subjects who have received local-regional therapy such as (but not limited to) chemoembolization, embolization, cryoablation, hepatic artery therapy, percutaneous ethanol injection, radiation therapy, radiofrequency ablation or surgery are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ? % in size. Local-regional therapy must be completed at least weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy. Hepatic radiation, chemoembolization, and radiofrequency ablation < weeks prior to study day . Patients may not have received prior systemic or hepatic directed infusional/embolization therapies for advanced uveal melanoma; local therapies such as radiofrequency ablation or cryotherapy for metastatic disease are permitted but must have been performed at least days prior to initiation of study therapy; lesions treated with local modalities such as radiofrequency ablation or cryotherapy may not be used as target lesions unless they demonstrate growth over a minimum of months on subsequent imaging studies Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >= weeks prior to randomization Progressive disease if treated with chemotherapy, radiotherapy, surgery or immunotherapy. If prior radiation was given, the measurable disease should be outside the radiation port. Unequivocal progression of HCC/BTC lesions previously treated with catheter-based therapy including transarterial chemoembolization or radioembolization is allowed. Must have had no previous systemic anti-cancer treatment, though previous loco-regional therapy is allowed: a. Prior treatment with any of the following is allowed: trans-arterial embolization, trans-arterial chemo-embolization, percutaneous ethanol injection, radio-embolization, radio-frequency ablation, or other ablation techniques. Prior chemoembolization, radioembolization, radiofrequency ablation (RFA) or other local ablative therapies are permissible if >= weeks from procedure with evidence of progression or new metastatic disease, if applicable No previous systemic anti-cancer therapy permitted ( prior systemic anti-cancer regimen are allowed in Phase Ib). Previous chemoembolization, radioembolization, radiofrequency ablation, or other local ablative therapies are permitted if greater than weeks of first day of study-defined treatment; Underwent resection, radiofrequency ablation, radiation or chemoembolization within weeks before enrollment or not recovered from such treatments. The participant is no longer a candidate for surgery, embolization, or radiofrequency ablation therapy Patients must have recovered from the acute effects of prior liver-directed therapy (e.g., radiation therapy [RT], radiofrequency ablation [RFA], MWA or transarterial chemoembolization [TACE]) and a minimum of weeks must have passed since the last procedure and protocol therapy Prior embolization, chemoembolization, or radiofrequency ablation permitted if >= weeks from registration and evidence of new tumor growth is present Patients must have completed prior (non-excluded) anti-cancer therapy (including surgery or chemotherapy or hepatic embolization/chemoembolization or radioactive isotopes i.e. yttrium ) at least weeks prior to day Subjects having had prior ablation therapy on the same tumor Liver-directed therapy (hepatic artery chemoembolization [HACE], hepatic artery embolization [HAE], selective internal radiation therapy [SIRT]) or peptide receptor radionuclide therapy (PRRT) =< days of first dose of study drug Documentation of complete ablation of BE after radiofrequency ablation on two endoscopic examinations at least months apart (including no evidence of BE on surveillance biopsies) as determined by the pathologist at each site; completion of ablation should have occurred no greater than months prior to randomization Prior hysterectomy or endometrial ablation Patients who have already received tumor treatment (either systemic or loco-regional such as previous YRE, microwave or radiofrequency [RF] ablation or transarterial chemoembolization [TACE]) Subjects must be scheduled to undergo transarterial chemoembolization (TACE) Participants who have had chemotherapy, radiofrequency ablation, microwave ablation, chemo-embolization, or radiotherapy within weeks prior to entering the study Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation or chemoembolization must show evidence of progressive disease based on RECIST . to be deemed a target lesion. Criteria , Participant is currently receiving or has received liver metastatic-directed therapy ( eg: radiation, ablation, embolization) less than wks prior to enrollment or hepatic surgery