Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension)
History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
Patients with known history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible:\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mmHg\r\n* NOTE: ophthalmic exam is required for all patients; exam must be obtained within 28 days prior to registration
A history or current evidence of retinal vein occlusion (RVO) including:\r\n* History of RVO or\r\n* Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mmHg as measured by tonography
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg.
History of or current evidence of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED\r\n* Current evidence of visible retinal pathology as assessed by pre-study ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of visual field defects, and/or intraocular pressure > 21 mm Hg
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a high risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
Has a history of RVO.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History of central serous retinopathy (CSR) or retinal vein occlusion (RVO), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm mercury (Hg)
Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes)
Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e., uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes)
Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes)
History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History or current evidence or retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)
TREATMENT: Patients with a history or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes), are ineligible to receive treatment with trametinib DMSO; visible retinal pathology (as assessed by ophthalmic exam) that is considered a risk factor for RVO or RPED includes evidence of new optic disc cupping or new visual field defects, or intraocular pressure > 21 mm Hg
History of or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
Central serous retinopathy (CSR) including presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or visible pathology (e.g., evidence of optic disc cupping, evidence of new visual field defects on automated perimetry, or intraocular pressure > 21 mmHg as measured by tonography) as assessed by ophthalmic examination
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or major predisposing factors to CSR or RVO (e.g. uncontrolled glaucoma or ocular hypertension) in the opinion of the study ophthalmologist
Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes)
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, history of hyperviscosity or hypercoagulability syndromes; visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
Patients with known history or current evidence of retinal vein occlusion (RVO) are not eligible:\r\n* History of RVO, or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mmHg\r\n** NOTE: Ophthalmic exam is required for all patients; exam must be obtained within 28 days prior to registration
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED): \r\n* Predisposing factors to RVO or RPED (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mm Hg
Patients with a known history of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyper viscosity or hypercoagulability syndromes)
Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as: \r\n* Evidence of new optic disc cupping \r\n* Evidence of new visual field defects \r\n* Intraocular pressure > 21 mm Hg as measured by tonography
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History or current evidence of retinal pigment epithelial detachment (RPED), retinal vein occlusion (RVO), or predisposing factors to RPED or RVO (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes)
A history or current evidence/risk of Retinal Vein Occlusion (RVO) or Central Serous Retinopathy (CSR) including: History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes); or Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as: Evidence of new optic disc cupping; Evidence of new visual field defects; Intraocular pressure >21 mmHg as measured by tonography.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes), or
Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping; Evidence of new visual field defects on automated perimetry; Intraocular pressure >21 mmHg as measured by tonography
History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:\r\n* Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)
GROUP 2 (trametinib arm): History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects  \r\n** Intraocular pressure > 21 mm Hg
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below =< 360 days prior to study entry\r\n* Pathologically (histologically or cytologically) proven diagnosis of HCC\r\n* At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava [IVC] and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis\r\n* For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI, in a patient with known HCC (diagnosed previously < 720 days)
Absence of occlusive main portal vein thrombus, branch venous thrombus is allowed
Main portal vein tumor thrombosis
Thrombosis of the main portal vein
Main portal vein vascular invasion; for the dose escalation, segmental portal vein is allowed
Subjects must be considered poor prognosis by the following parameters: 1) right or left portal vein involvement (NOTE: subjects with main portal vein involvement are excluded), 2) multi-focal disease (more than 3 tumors regardless of size) AND/OR 3) diffuse disease considered amenable to liver directed therapy
Complete portal vein occlusion
Color Doppler ultrasonography showing portal vein tumor thrombosis with complete main portal vein obstruction without cavernous transformation; or obstructive jaundice
Occlusion of the main portal vein, or inadequate collateral flow around an occluded portal vein as determined by angiography
Main portal vein thrombosis (Vp4) as documented on imaging
Locally advanced, unresectable pancreatic cancer as determined by a pancreaticobiliary surgeon as part of a multidisciplinary discussion at MDACC, including triphasic CT demonstrating tumor abutment of the superior mesenteric artery (SMA) or celiac axis, superior mesenteric vein (SMV) or portal vein (PV) involvement which is not resectable without vascular reconstruction.
Patients with portal vein invasion
Patients with portal vein thrombus
Main portal vein tumor thrombus
Complete portal vein thrombosis on CT scans
Portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on CT as having tumor abutment of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement
Resectable primary tumor of the head, body or tail of the pancreas defined per National Comprehensive Cancer Network (NCCN) guidelines version 2.2015:\r\n* No extra-pancreatic disease, aside from lymphadenopathy\r\n* No arterial tumor contact (celiac axis, superior mesenteric artery, or common hepatic artery)\r\n* No tumor contact with the superior mesenteric vein or portal vein or =< 180 degree contact without vein contour irregularity
There should be no macroscopic intravascular invasion of tumors into the main portal vein, hepatic vein, or vena cava.
Patients with extrahepatic disease, portal hypertension, or bilobar disease are allowed
Tumors must be localized (non-metastatic) and classified as borderline resectable according to Americas Hepato-Pancreato-Biliary Association (AHPBA)/Society of Surgical Oncology (SSO)/Society for Surgery of the Alimentary Tract (SSAT) consensus criteria or be clinically node-positive via computed tomography (CT) or endoscopic ultrasound\r\n* AHPBA/SSO/SSAT criteria (any one of the following):\r\n** Tumor-associated deformity of the SMV (superior mesenteric vein) or PV (portal vein)\r\n** Abutment of the SMV or PV >= 180 degrees\r\n** Short-segment occlusion of the SMV or PV amenable to resection and venous reconstruction\r\n** Short-segment involvement of the hepatic artery or its branches amenable to resection and reconstruction\r\n** Abutment of the superior mesenteric artery (SMA) < 180 degrees
All patients must be staged with a physical exam, computed tomography (CT) of the chest and contrast-enhanced helical thin-cut abdominal CT; unresectability is defined by CT criteria: \r\n* Evidence of tumor extension to the celiac axis or superior mesenteric (SM) artery, or \r\n* Evidence on either CT or angiogram of occlusion of the SM vein or SM/portal vein confluence
Barcelona Clinic Liver Cancer stage B or C; segmental and subsegmental portal vein thrombosis is allowed
Unresectable disease or borderline resectable disease assessed by a multidisciplinary panel of pancreas surgeon, medical and radiation oncologist, and a radiologist; criteria defining unresectable and borderline resectable patients will be based on the National Comprehensive Cancer Network (NCCN) Guidelines (version [v] 1.2014)\r\n* Unresectable\r\n** Greater than 180 degrees of superior mesenteric artery (SMA) encasement\r\n** Any celiac abutment\r\n** Unreconstructible superior mesenteric vein (SMV)/portal occlusion\r\n** Aortic invasion or encasement\r\n** Nodal metastases beyond the field of resection\r\n* Borderline resectable\r\n** Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen\r\n** Encasement of the SMV/portal vein but without encasement of the nearby arteries\r\n** Short-segment venous occlusion resulting from either tumor thrombus or encasement with suitable proximal and distal vessel for reconstruction/grafting.\r\n** Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to celiac axis\r\n** Tumor abutment to SMA but not to exceed greater than 180 degrees of circumferential vessel wall
Borderline-resectable or locally-advanced pancreatic cancer (based upon impression of the surgical oncologist, in conjunction with radiologic consultations) as defined per the Alliance consensus:\r\n* Borderline-resectable\r\n** An interface between the primary tumor and superior mesenteric vein (SMV)/portal vein measuring 180 degrees or greater of the circumference of the vein wall\r\n** Short-segment occlusion of the SMV/portal vein but with suitable vessel proximal and distal to the obstruction to allow safe resection and reconstruction\r\n** Short-segment interface (of any degree) between the tumor and the hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction\r\n** An interface between the tumor and the superior mesenteric artery (SMA) or celiac trunk measuring less than 180 degrees of the circumference of the artery wall \r\n* Locally-advanced\r\n** Encasement of the SMA/celiac artery (> 180 degrees)\r\n** Involvement of the SMV/portal vein without options for reconstruction\r\n** Aortic invasion or encasement
Absence of occlusive thrombus in the main portal vein
Have portal or hepatic vein tumor invasion/thrombosis.
Resectable pancreatic adenocarcinoma disease as defined as follows:\r\n* No evidence of extrapancreatic disease by cross sectional imaging, PET scan, or laparoscopy, including nodal involvement beyond the peripancreatic tissues and/or distant metastases;\r\n* No evidence of tumor extension to superior mesenteric artery, hepatic artery, celiac axis, aorta, or inferior vena cava, and no evidence of occlusion or encasement of the superior mesenteric vein or superior mesenteric vein/portal vein confluence, as assessed by computed tomography (CT) using pancreatic protocol (or magnetic resonance imaging [MRI] in patients who cannot undergo CT) and EUS
Patients will have unresectable disease, defined radiographically as > 180 degrees involvement of the superior mesenteric artery or celiac trunk or superior mesenteric vein (SMV)/portal vein impingement that cannot be surgically reconstructed, in the absence of distant metastasis
Borderline resectable per National Comprehensive Cancer Network (NCCN) criteria (no distant metastases, venous involvement of the portal vein/superior mesenteric vein [SMV], demonstrating tumor abutment and narrowing of the lumen, encasement of the portal vein/SMV without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal or distal to this area of vessel involvement, allowing for safe resection and reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; tumor abutment of the superior mesenteric artery [SMA] not to exceed 180 degrees of the circumference of the vessel wall)
Disease should be determined as \borderline resectable\ according to the Expert Consensus Statement published by Callery et al:\r\n* No distant metastasis\r\n* Venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction\r\n* Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis\r\n* Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall
Patients with a history of gastrinoma, hepatic vasculature incompatible with perfusion, hepatofugal flow in the portal vein or known unresolved venous shunting.
Portal vein occlusion
Complete occlusion of the main portal vein.
Ascites, or complete occlusion of main portal vein
Portal hypertension with portal venous shunt away from the liver
Portal hypertension with portal venous shunt away from the liver
Tumor thrombus involving main trunk of portal vein or inferior vena cava
Invasion of the main portal vein and/or tumor involvement in more than 50% of the liver (applicable only for the dose-escalation part)
Patients with Portal-caval shunts
No macroscopic intra-vascular invasion by tumors of the main portal vein, hepatic vein or vena cava.
Thrombotic or embolic event within the last 6 months including portal vein thrombosis
ARM B: Patients must not have clinically significant ascites and/or portal vein thrombosis
Macrovascular tumor invasion of portal and/or hepatic vein(s)
Significant hepatic arterial to portal vein shunting in the area to be treated
No segmental, lobar or main portal vein thrombosis as evidence by cross sectional imaging
Splanchnic vein thrombosis (includes Budd-Chiari, portal vein, splenic and mesenteric thrombosis)
Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
Patients must have resectable primary tumor based on contrast-enhanced CT or MRI (CT or MRI without contrast as part of positron emission tomography [PET]/CT or PET/MRI is NOT acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is acceptable) of the chest, abdomen, and pelvis; the local interpreting radiologist must review the scans and sign the S1505 local radiology checklist prior to registration; resectable is defined as:\r\n* No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery)\r\n* No involvement, or < 180 degrees interface between tumor and vessel wall, of the portal vein and/or superior mesenteric vein; and patent portal vein/splenic vein confluence\r\n* No evidence of metastatic disease; lymphadenopathy (defined as nodes measuring > 1 cm in short axis) outside the surgical basin (i.e., para-aortic, peri-caval, celiac axis, or distant nodes) is considered M1 disease and makes the patient ineligible; if, however, such nodes are biopsied and are negative, then enrollment can be considered after review with the study chairs\r\n* Note: for tumors of the body and tail of the pancreas, involvement of the splenic artery and vein of any degree is considered resectable disease
Main portal vein thrombosis
Has portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
Portal vein invasion at the main portal branch (Vp4)
No portal invasion or extrahepatic spread
One of the following:\r\n* Upfront resectable disease; this is defined as:\r\n** No arterial tumor contact (celiac axis [CA], superior mesenteric artery [SMA], or common hepatic artery [CHA]); AND\r\n** No tumor contact with the superior mesenteric vein (SMV) or portal vein (PV), or =< 180 degree contact without vein contour irregularity\r\n* Borderline resectable disease; There are multiple definitions of borderline resectable PDAC including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract; borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612); per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on CT or MRI:\r\n** An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring >= 180 degrees of the circumference of the vessel wall\r\n** Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction\r\n** Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction\r\n** An interface between the tumor and SMA measuring < 180 degrees of the circumference of the vessel wall
Locally advanced, unresectable pancreatic cancer defined on post-induction chemotherapy computed tomography (CT) as having tumor involvement of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or pemphigus vulgaris (PV) involvement
Patients with occlusion of the main portal vein or of the right and left portal branches
Main portal vein thrombosis (PVT)
Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
Head: Greater than 180 degrees SMA encasement or any celiac abutment or unreconstructible SMV/portal occlusion or aortic invasion or encasement.
Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible SMV/portal occlusion or aortic invasion.
Patients with locally advanced, unresectable disease will be included; locally advanced unresectable disease is defined by the National Comprehensive Cancer Network (NCCN) as:\r\n* Tumors of the head that have greater than 180 degrees of superior mesenteric artery (SMA) encasement or any celiac abutment, unreconstructable superior mesenteric vein (SMV) or portal occlusion, or aortic invasion or encasement\r\n* Tumors of the body with SMA or celiac encasement of greater than 180 degrees, unreconstructable SMV or portal occlusion, or aortic invasion\r\n* Tumors of the tail with SMA or celiac encasement of greater than 180 degrees\r\n* Irrespective of location, all tumors with evidence of nodal metastasis outside of the resection field are deemed unresectable
A patent superior mesenteric (SMV)- portal vein (PV) confluence (assuming the technical ability to resect and reconstruct this venous confluence if needed)
Active infections including hepatitis B and hepatitis C; definition of active hepatitis C infection include:\r\n* Positive hepatitis C virus (HCV) ribonucleic acid (RNA) viral load by quantitative polymerase chain reaction (PCR) testing or if negative HCV RNA viral load BUT on antiviral treatment\r\n* Liver biopsy with pathologic evidence of \r\n** Necrosis and inflammation around the portal areas - piecemeal necrosis or interface hepatitis or necrosis of hepatocytes and focal inflammation in the liver parenchyma\r\n** Inflammatory cells in the portal areas (\portal inflammation\)\r\n** Fibrosis, with early stages being confined to the portal tracts, intermediate stages being expansion of the portal tracts and bridging between portal areas or to the central area, and late stages being frank cirrhosis characterized by architectural disruption of the liver with fibrosis and regeneration
Patients who are deemed \borderline resectable\ will be included; borderline resectable is defined by the NCCN as tumors with venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection or reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; or tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall; tumors involving retroperitoneal structures that can be surgically removed (ie. kidney), will also be included
Occlusion of the main portal vein, or inadequate collateral flow around an occluded branch of the portal vein as determined by angiography
Patients must have borderline resectable pancreatic adenocarcinoma defined by one of the following criteria: \r\n* Tumor associated deformity of the superior mesenteric vein (SMV) or portal vein (PV) \r\n* Abutment of the SMV or PV =< 180 degrees \r\n* Short-segment occlusion of the SMV or PV amenable to resection and venous reconstruction \r\n* Short-segment involvement of the hepatic artery or its branches amenable to resection and reconstruction or \r\n* Abutment of the superior mesenteric artery (SMA) =< 180 degrees
No portal invasion or extrahepatic spread on imaging.
Advanced tumoral disease (vascular invasion or extrahepatic spread, portal vein thrombosis of bland or malignant origin), or diffuse HCC, defined as 50% liver involvement).
Portal vein thrombosis of bland or malignant origin.
Macrovascular invasion of lobar portal vein branches or main portal vein.
Venous involvement of the SMV/portal vein demonstrating tumor abutment with impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short-segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
Head: Greater than 180 degrees SMA encasement or any celiac abutment or unreconstructible SMV/portal occlusion or aortic invasion or encasement.
Body: Greater than 180 degrees SMA or celiac encasement or unreconstructible SMV/portal occlusion or aortic invasion.
Presence of main portal vein invasion by liver cancer
Evidence of hepatic vein invasion or caval thrombosis
Definition of localized, potentially resectable disease:\r\n* Staging by intravenous contrast-enhanced thin section helical abdominal computed tomography (2.5 mm cuts or less) or magnetic resonance imaging (MRI) (for patients with an IV contrast allergy) using pancreatic protocol; endoscopic ultrasound is required for tissue acquisition and staging confirmation\r\n* No extension to superior mesenteric artery (SMA) and hepatic artery; patent superior mesenteric vein/portal vein (SMV/PV) with < 180-degree abutment and no evidence of invasion\r\n* Clear fat plane between the SMA and celiac axis\r\n* No extension to celiac axis and hepatic artery\r\n* Patent superior mesenteric vein and portal vein\r\n* No evidence of distant disease
Borderline resectable disease as defined by:\r\n* Staging by intravenous contrast-enhanced thin section helical abdominal computed tomography (2.5 mm cuts or less) or magnetic resonance imaging (MRI) (for patients with an IV contrast allergy) using pancreatic protocol; endoscopic ultrasound is required for tissue acquisition and staging confirmation:\r\n** American Joint Committee on Cancer (AJCC) stage II\r\n** May have abutment of the superior mesenteric artery (SMA); abutment must be < 180\r\n** Abutment of the celiac axis\r\n** May have abutment or short segment encasement of the common hepatic artery (CHA) \r\n** May have short segment occlusion of the superior mesenteric vein (SMV)-portal vein (PV) confluence if reconstruction is possible\r\n** No evidence of distant disease
Locally advanced, unresectable pancreatic cancer as confirmed by the multidisciplinary input from a hepatobiliary surgeon and as defined on computed tomography (CT) as having tumor abutment of > 180 degrees (> 50%) of the circumference of the superior mesenteric artery (SMA) or celiac axis, unreconstructable superior mesenteric vein (SMV) or portal vein (PV) involvement
Patients must have resectable pancreatic cancer OR must be deemed borderline resectable; potentially resectable is defined as a) no extrapancreatic disease, b) no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery (SMA),and c) no evidence (CT or MRI) of occlusion of the superior mesenteric vein (SMV) or superior mesentericportal vein (SMPV) confluence; borderline resectable is defined by the National Comprehensive Cancer Network (NCCN) as tumors with venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection or reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; or tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall; tumors involving retroperitoneal structures that can be surgically removed (ie. kidney), will also be included
Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis; surgically related ascites does not exclude the patient)
Evidence of ascites, cirrhosis, portal hypertension, main portal or venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
History of main or lobar portal vein thrombosis
Contraindications to hepatic artery embolization:\r\n* High risk of hepatic failure, indicated by the constellation of greater than 50% liver replacement by tumor, lactate dehydrogenase (LDH) > 425 mU/ml, serum glutamic-oxaloacetic transaminase (SGOT)(aspartate aminotransferase [AST]) > 100mU/ml; and bilirubin > 2 mg/dl\r\n* Portal vein occlusion without hepatopetal collateral flow demonstrated by angiography; or portal hypertension with hepatofugal flow\r\n* Hepatic encephalopathy
Confirmed acute lower extremity or upper extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis
Resectable pancreatic ductal adenocarcinoma (R-PDAC): no evidence of distant metastasis and tumor mass showing no extension to superior mesenteric artery (SMA) and hepatic artery; there must be a clearly defined fat plane between SMA and celiac axis; patent superior mesenteric vein (SMV/portal vein [PV]) with no distortion of venous architecture
Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC): defined as localized PDAC with 1 or more of the following features: a) an interface between the primary tumor and superior mesenteric vein (SMV)-portal vein (PV) measuring 180 degrees or greater of the circumference of the vein wall, and/or b) short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction and/or c) short-segment interface of any degree between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction and/or d) an interface between the tumor and SMA or celiac trunk measuring less than 180 degrees of the circumference of the artery wall
Occlusive main portal vein thrombosis
Main or segmental portal vein thrombosis
Clinically referred for portal vein embolization
Criteria 3, There is invasion by cancer into the main blood vessels such as the portal vein, hepatic vein or the vena cava
History or current evidence/risk of retinal vein occlusion (RVO)
Patients must not have history of retinal vein occlusion (RVO)
Patients with a previously documented retinal vein occlusion
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History of prior or current retinal vein occlusion (RVO)
Known history of retinal vein occlusion (RVO).
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
STRATUM B: Participants with retinal vein occlusion (RVO)
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration. Patients should be excluded if they have the following risk factors for RVO:\r\n* History of serous retinopathy.\r\n* History of retinal vein occlusion (RVO).\r\n* Evidence of ongoing serous retinopathy or RVO at baseline.
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
Patients will not be eligible if they have a history of retinal vein or artery occlusion
A history or current evidence of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History or current evidence/risk of retinal vein occlusion (RVO)
History of retinal degenerative disease, history of uveitis, history of retinal vein occlusion (RVO), or any eye condition that would be considered a risk factor for RVO or has medically relevant abnormalities identified on screening ophthalmologic examination
A history of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
A history of retinal vein occlusion (RVO) or risks factors for RVO
History of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
Patient must not have a history of retinal vein occlusion (RVO)
Patients with a history or current evidence/risk of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History of retinal vein occlusion
Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO
History of or current evidence of retinal vein occlusion (RVO) or risk factors of RVO
History of retinal vein occlusion (RVO)
A history or current evidence of retinal vein occlusion (RVO).
History or current evidence/risk of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal vein occlusion
Predisposing factors to retinal vein occlusion (RVO)
History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History of or current evidence of retinal vein occlusion (RVO).
History or current evidence/risk of retinal vein occlusion (RVO)
Patients with a history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Patients who meet any of the following exclusion criteria related to ocular disease will be excluded from study entry:\r\n* Known risk factors for ocular toxicity, consisting of any of the following:\r\n** History of serous retinopathy\r\n** History of retinal vein occlusion (RVO)\r\n** Evidence of ongoing serous retinopathy or RVO at screening
History or evidence of ongoing serous retinopathy or retinal vein occlusion (RVO) at baseline
Patients with a history or current evidence of CSR (central serous retinopathy), RVO (rential vein occlusion), or ophthalmopathy present at baseline that would be considered a risk factor for CSR or RVO
A history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Ophthalmological conditions as follows:\r\n* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion\r\n* Uncontrolled glaucoma (irrespective of intraocular pressure [IOP])
History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing serous retinopathy or RVO at baseline
Known risk factors for ocular toxicity, consisting of any of the following:\r\n* presence of serous retinopathy within 6 months of protocol enrollment\r\n* presence of retinal vein occlusion (RVO) within 6 months of protocol enrollment.
Any corneal or retinal abnormality likely to increase the risk of eye toxicity, such as:\r\n* Current corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration\r\n* Uncontrolled glaucoma despite standard of care therapy\r\n* Diabetic retinopathy with macular edema\r\n* Known active wet, age-related macular degeneration (AMD)\r\n* Known central serous retinopathy (CSR) or retinal vascular occlusion (RVO)
Ophthalmological conditions as follows: current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion; or intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)
Patients with known history of serous retinopathy will not be eligible
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Ophthalmological conditions as follows: \r\n• Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure) \r\n• Current or past history of central serous retinopathy or retinal vein occlusion
Patients with the following ophthalmological findings/conditions:\r\n* Intraocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure)\r\n* Current or past history of central serious retinopathy or retinal vein occlusion
History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO)
History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)
Ophthalmological conditions as follows:\r\n* Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)\r\n* Current or past history of central serous retinopathy or retinal vein occlusion
History of or current evidence / risk of retinal vein occlusion (RVO) central serous retinopathy (CSR), or glaucoma with intraocular pressures ? 21 mmHg or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities
Ophthalmologic conditions, including any of the following:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma
Known ophthalmological conditions as follows: intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure); current or past history of central serous retinopathy or retinal vein occlusion
CLINICAL/LABORATORY CRITERIA: Patients must not have untreated or unresolved retinopathy or have a history (or current evidence) of retinal vein occlusion determined by an ophthalmology exam within 42 days prior to registration
History of predisposition to retinal vein occlusion or central serous retinopathy
History of predisposition to retinal vein occlusion or central serous retinopathy
History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease
Patients with a history or current known evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy at baseline that would be considered a risk factor for CSR or RVO
A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
History of central serous retinopathy or retinal vein occlusion
Patients with baseline risk factors for central serous retinopathy or retinal vein occlusion such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR)
A history or current evidence/risk of retinal vein occlusion (RVO) or Central serous retinopathy (CSR) including
History of retinal vein occlusion, central serous retinopathy or glaucoma.
Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein occlusion or central serous retinopathy.
History or evidence of retinal pathology according to protocol-defined criteria, including serous retinopathy
Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination.
Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible
Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, RVO (retinal vein occlusion), or neovascular macular degeneration; the risk factors for RVO are listed below; patients should be excluded if they have the following current conditions: \r\n* Uncontrolled glaucoma with intra-ocular pressures > 21 mmHg \r\n* Serum cholesterol > grade 2 \r\n* Hypertriglyceridemia > grade 2 \r\n* Hyperglycemia (fasting) > grade 2
History of retinal vein occlusion, neurosensory retinal detachment, or neovascular macular degeneration. Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment.
Patients with history of retinal vein oclusion.
History of current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma; intra-ocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma
Clinically relevant retinal abnormalities as per the medical history or ophthalmologic findings in the pretreatment evaluation (e.g., retinitis pigmentosa or macular degeneration).
Participants with evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Participants with a history of or current evidence of retinal vein occlusion or retinal pigment epithelial detachment
Have a degenerative retinal disease. Retinal diseases that require a subject's exclusion include: glaucoma, hereditary retinal diseases such as retinitis pigmentosa; retinal arterial occlusive disease; and retinal disease with advanced scarring, to include age-related macular degeneration and myopic degeneration with geographic atrophy.
Subjects with any retinal abnormalities, including subjects with diabetic retinopathy, macular degeneration, or other known forms of retinal degenerative disease
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Evidence of visible retinal pathology on screening ophthalmologic examination that places the participant at an unacceptable risk for retinal vein occlusion (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, etc.)
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Presence of neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration on screening ophthalmologic exam
EXPANDED ACCESS COHORT: Presence of neurosensory retinal detachment or retinal vein occlusion (RVO) on screening ophthalmologic exam
Participants with evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration Cardiac Exclusion Criteria:
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
Have history or findings of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study.
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
History of or evidence of retinal pathology on baseline ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
Corneal or retinal abnormality likely to increase the risk of eye toxicity
History of retinal degenerative disease
Presence of retinal disease in the eye that is not due to neovascular age-related macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal atrophy, retinal detachment).
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration; patients will be excluded from study participation if they are currently known to have any of the following risk factors for RVO:\r\n* Glaucoma with intraocular pressure >= 21 mmHg\r\n* Grade >= 2 serum cholesterol (patients with a history of elevated cholesterol controlled with lipid lowering medication to grade =< 1 are eligible)\r\n* Grade >= 2 hypertriglyceridemia (patients with a history of elevated cholesterol controlled with lipid lowering medication to grade =< 1 are eligible)\r\n* Grade >= 2 or symptomatic hyperglycemia (fasting); hyperglycemia may be corrected with medications to grade =< 1\r\n* Grade >= 2 uncontrolled hypertension (patients with a history of hypertension controlled with anti-hypertensive medication to grade =< 1 are eligible)
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
No prior known history of retinal neovascularization, macular edema or macular degeneration; patients without such a history are required to have a baseline ophthalmologic exam as part of screening, and must not have evidence of retinal neovascularization, macular edema or macular degeneration on the screening exam in order to be eligible
Ocular:\r\n* History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusions (RVO), or neovascular macular degeneration\r\n* The risk factors for RVO are listed below; patients should be excluded if they have the following current conditions:\r\n** Uncontrolled glaucoma with intra-ocular pressures > 21 mmHg\r\n** Serum cholesterol >= grade 2\r\n** Hypertriglyceridemia >= grade 2\r\n** Hyperglycemia (fasting) >= grade 2
History of or evidence of retinal pathology or ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible
History of significant or major funduscopic findings including, but not limited to, retinal exudates, hemorrhage, detachment, neovascularization, papilledema, optic atrophy, micro-aneurysm or macular changes
Patients with macular edema, retinal vein occlusion or retinal hemorrhage are excluded
History of retinal degenerative disease
Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
A history of retinal pigment epithelial detachment (RPED) or risk factors for RPED
History of retinal disease as defined in the protocol.
Active retinal pigment epithelium (RPE)/photoreceptor disorders such as; retinitis pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease (STGD), macular degeneration.
Ocular exclusion criteria:\r\n* History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion or neovascular macular degeneration\r\n* Patients will be excluded if they have the following risk factors for retinal vein occlusion: Uncontrolled glaucoma with intraocular pressure >= 21 mmHg. Serum cholesterol >= grade 2. Hypertriglyceridemia >= grade 2. Hyperglycemia (fasting) >= grade 2
History of retinal degenerative disease
History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/CSCR, RVO, or neovascular macular degeneration
History of retinal degenerative disease
Patients must not have any of the following ophthalmological criteria: current evidence or previous history of retinal pigmented epithelium detachment (RPED); previous laser treatment or intra-ocular injection for treatment of macular degeneration; current evidence or previous history of dry or wet age-related macular degeneration; current evidence or previous history of retinal vein occlusion (RVO); current evidence or previous history of retinal degenerative diseases (e.g. hereditary); or current evidence or previous history of any other clinically relevant chorioretinal defect
Patients must not have any of the following ophthalmological criteria: current evidence or previous history of retinal pigmented epithelium detachment (RPED); previous laser treatment or intra-ocular injection for treatment of macular degeneration; current evidence or previous history of dry or wet age-related macular degeneration; current evidence or previous history of retinal vein occlusion (RVO); current evidence or previous history of retinal degenerative diseases (e.g. hereditary); or current evidence or previous history of any other clinically relevant chorioretinal defect; patients must have an eye exam performed within 28 days prior to Step 2 re-registration; patients with uncontrolled glaucoma or intra-ocular pressure >= 21 mm Hg at screening should be referred for ophthalmological management and the condition controlled prior to crossover registration
History or current evidence/risk of visual loss syndromes, including but not limited to retinal vein occlusion (RVO), retinal detachment, macular degeneration, or visual migraine headaches
Retinal disease or a history of retinal disease or detachment
Retinal disease (e.g. retinitis pigmentosa including Mertk mutations), retinal hemorrhage or any disorder which may inhibit follow up for retinal toxicity
For participants to be enrolled into the vemurafenib+cobimetinib+ atezolizumab cohorts: history of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
History of retinal degenerative disease
History of retinal degenerative disease
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
Evidence of visible retinal pathology on screening ophthalmologic examination that places the participant at an unacceptable risk for ocular toxicity, such as risk factors for retinal vein occlusion, related to PD-0325901
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Has retinal degenerative disease
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration; the risk factors for RVO are listed below; patients should be excluded if they have the following conditions:\r\n* Uncontrolled glaucoma with intra-ocular pressures > 21mmHg\r\n* Serum cholesterol >= grade 2\r\n* Hypertriglyceridemia >= grade 2\r\n* Hyperglycemia (fasting) >= grade 2
Retinal pathology beyond normal age-related processes
History of retinal degenerative disease
History of retinal degenerative disease
Patients with pre-existing retinal disease on ophthalmologic exam will be excluded
Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis
History of RVO, neurosensory retinal detachment, or neovascular macular degeneration
History of retinal degenerative disease
A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met.
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioetinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:
The patient has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion, or history of retinal detachment, or has medically relevant abnormalities identified on screening ophthalmologic examination.
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma
The subject has a history of retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), uveitis or retinal vein occlusion (RVO), or has other relevant abnormalities identified on screening opthalmologic examination, which may increase the risk of serous retinal detachment (SRD) or RVO.
Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
Unacceptable ocular/retinal conditions
No underlying ocular/retinal pathology.
History of retinal degenerative disease
Blind or having a history of eye disease including, but not limited to, macular degeneration, or other diagnosed retinal problems
Patients with a history of retinal disease
Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment
History of retinal vein occlusion (RVO), neurosensory retinal detachment, or neovascular macular degeneration