History of bleeding esophageal varices in previous 6 months, which have not been adequately managed with banding or sclerotherapy.
Subjects with a history of esophageal bleeding have varices that have been sclerosed or banded and no bleeding episodes have occurred during the prior 6 months.
Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
Phase 1a: ISH positive or IHC 3+ advanced cancer (including breast or gastric/esophageal or other solid tumors).
Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.
Histologically proven (squamous cell or adenocarcinoma) esophageal or gastro- esophageal junction cancer (core biopsy required)
Diagnosed with cervical esophageal carcinoma
Evidence of hepatic decompensation including esophageal or gastric variceal bleeding or hepatic encephalopathy
History of esophageal varices
COHORT B, GROUP 6: HEPATOCELLULAR CARCINOMA: Patients with evidence of portal hypertension must have had an esophagogastroduodenoscopy (EGD) within last year with appropriate treatment of esophageal varices as per standard of care
Diagnosis of cervical esophageal carcinoma
Any prior anticancer therapy for esophageal cancer
If clinical or histologic diagnosis of cirrhosis and/or clinical or radiographic evidence esophageal or gastric varices, must have had esophagogastroduodenoscopy (EGD) surveillance and adequate endoscopic therapy according to institutional standards
History of upper gastrointestinal (GI) bleeding from esophageal and/or gastric varices within 12 months before enrollment
The patient has undergone any facial, esophageal, gastric or sinus surgery within the last 3 months.
GI Bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
Untreated or poorly controlled gastro-esophageal reflux disease
Impaired synthetic function or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, ascites, and bleeding from esophageal varices
Previous esophageal dilatation is permitted, provided the patient has developed recurrent dysphagia since that procedure
Prior history of esophageal perforation
Evidence of severe portal hypertension by history, endoscopy, or radiologic studies\r\n* Note: Any diagnosis of portal hypertension or clinical stigmata of such including but not limited to gastric or esophageal varices, umbilical vein varices or telangiectasias
Histologically or cytologically confirmed diagnosis of advanced stage gastric, gastro-esophageal, or esophageal cancers in whom ramucirumab and paclitaxel are reasonable treatments
Has had esophageal or gastric variceal bleeding within the last 6 months; all subjects will be screened for esophageal varices, unless such screening has been performed in the past 12 months before first dose of treatment; if varices are present, they should be treated according to institutional standards before starting study treatment
A history of Common Toxicity Criteria (CTC) grade 3 bleeding esophageal or gastric varices within the past 2 months; prior variceal bleed is permitted if patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months; patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened (using either esophagogastroduodenoscopy [EGD] or capsule endoscopy) for esophageal varices, unless such screening has been performed in the past two years from study entry and the patient is receiving medical treatment for prophylaxis of variceal bleeding, such as non-selective beta blockade; if varices are identified that require intervention (banding), patient will not be eligible until varices are adequately treated; patients presenting with gastric varices will not be eligible for the study
Prior fistula within thorax, including bronchoalveolar or esophageal
Cervical esophageal cancer will not be entered in this study
Occurrence of esophageal or other gastrointestinal hemorrhage requiring transfusion within 4 weeks prior to the Baseline Visit.
Patient that is contraindicated to upper GI endoscopy and/or any procedure to be performed in conjunction with esophageal stent placement
Potentially resectable or unresectable esophageal cancer patients
Any patient deemed eligible for chemoradiation for esophageal cancer treatment
Patients with active second malignancy are allowed as long as it is determined by the treating physician that the treatment of esophageal cancer is of higher priority through proper evaluation; however patients with active stage 4, metastatic cancers, receiving other systemic therapies at the time of the esophageal cancer diagnosis, will not be eligible
Known varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer.
Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
Clinical evidence of portal hypertension with bleeding esophageal or gastric varices at Screening, or within 6 months before randomization
Hepatocellular carcinoma cohort specific exclusion criteria:\r\n* A history of hepatic encephalopathy within the past 12 months; patients on stable doses of lactulose for prophylaxis or as a result of previous hepatic encephalopathy (more than 12 months ago) are allowed (for HCC cohort only)\r\n* A history of bleeding esophageal or gastric varices within the last 6 months prior to initiation of study therapy
Evidence of severe portal hypertension by history, endoscopy, or radiologic studies\r\n* Note: any diagnosis of portal hypertension or clinical stigmata of such including but not limited to gastric or esophageal varices, umbilical vein varices or telangiectasias
Patients must not have had prior chemotherapy or radiation therapy for esophageal cancer
Patients with cervical esophageal carcinoma
Prior radiation therapy for esophageal cancer or prior chest radiotherapy
Has had esophageal or gastric variceal bleeding within the last 6 months.
History of high grade esophageal or gastric varices
History of high grade esophageal or gastric varices
gastric cancer (including gastro-esophageal junction)
Has had esophageal or gastric variceal bleeding within the last 6 months
Gastric or esophageal varices that require interventional treatment within 28 days prior to randomization. Prophylaxis with pharmacologic therapy (eg, nonselective beta-blocker) is permitted.
Portosystemic hypertension or known history of bleeding esophageal varices.
Participant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomization
Subject has a history of bleeding esophageal varices within 3 months before the Day 1 visit.
Gastric, GEJ or esophageal adenocarcinoma for which treatment with FOLFOX6, CAPOX, FOLFIRI, or irinotecan would be acceptable as determined by the Investigator.
Patients who have radiographic evidence of esophageal varices or history of variceal hemorrhage
Bleeding esophageal or gastric varices within 30 days prior to treatment initiation
Esophageal or gastric varices
History of Barrett's esophagus, esophageal webbing, stricture, or fistula
Patients must have histologically confirmed gastric, gastro-esophageal junction or distal esophageal adenocarcinoma (predominant histology) that is recurrent, metastatic or unresectable
Gastric or Gastro-Esophageal junction carcinoma (No longer enrolling this tumor type)
Esophageal variceal bleeding within 2 weeks prior to the first dose of TKM-080301.
Bleeding esophageal or gastric varices within 2 months before enrollment.
Patient has previously undergone esophageal stenting or esophagectomy
Patient has trouble swallowing or experiences regurgitation for reasons which are not related to his/her esophageal cancer
Esophageal or gastric variceal bleeding within last 3 months
Risk for varices, based on known history of esophageal or gastric varices, evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices
Known bleeding diathesis, esophageal varices, or angioplasty
Patients with a history of bleeding varices in previous 1 year are excluded (unless patient has subsequently had a liver transplant); those with gastric varices or varices that are deemed as high risk by the endoscopist should be placed on appropriate medical therapy as advised by the gastroenterologist
Known esophageal varices at risk of bleeding, including medium or large esophageal or gastric varices, or active peptic ulcer
Mean esophageal radiation dose > 45 Gy
Subjects with an esophageal stent in situ at the time of study enrollment
Subject has had previous Spray Cryotherapy for esophageal cancer.
Recent esophageal, gastric or bowel surgery (within 3 weeks of study enrollment)
Tracheo-esophageal fistula
Esophageal or gastric varices that require intervention or represent high bleeding risk. Participants with evidence of portal hypertension or prior bleeding must have had endoscopic evaluation within 3 months prior to randomization.
Presence of an esophageal or duodenal stent
Patients with known, untreated esophageal strictures, prior partial esophageal resection, or altered anatomy preventing passage of the endomicroscope
Patients diagnosed with any level of dysplasia on previous esophageal biopsies
Patients who had esophageal therapy with Halo radiofrequency ablation in the past, or esophagectomy
History of esophageal dysplasia or cancer
Esophageal ulcerations
Esophageal candida
Esophageal varices
Subjects with esophageal varices
Patients have no known coagulopathy and no known history of esophageal varices
Patients have known coagulopathies or history of esophageal varices
Patients with esophageal dysmotility
Prior history of esophageal cancer
Subjects may have a history of prior malignancy except for esophageal adenocarcinoma
Esophageal adenocarcinoma
Gastric and esophageal cancer
History of esophageal or gastric surgery
Presence of an esophageal stricture defined as “any recognizable change in esophageal luminal caliber that is accompanied by symptoms of dysphagia, or any asymptomatic narrowing that either will not allow any adult endoscope to pass or allows passage with resistance”
Patients with esophageal cancer receiving trastuzamab
Subjects with completely obstructing esophageal cancer
Subjects with known or suspected esophageal varices
Prior esophageal or gastric surgical resection.
Significant esophageal stricture requiring dilatation.
Previous esophageal procedure (surgery, photodynamic therapy, argon plasma coagulation, endoscopic mucosal resection)
Requires a clinically necessary esophagectomy for esophageal cancer or other indications.
Untreated esophageal varices observed on EGD or imaging study; however, patients with known portal hypertension and evidence of varices on EGD or imaging study who have undergone appropriate therapy as indicated within the last 6 months (if applicable) are eligible for enrollment.
Previous history of a swallowing disorder, such as scleroderma, achalasia, esophageal stricture or esophageal diverticulum