Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

Inclusion Criteria

• Patients must have histologically confirmed advanced or metastatic squamous adenocarcinoma of the esophagus, GEJ, or stomach
• Patients must have primary tumor and adjacent normal tissue accessible via endoscopic biopsy
• Patients must have received at least one prior chemotherapy regimen for their unresectable or metastatic disease, not including treatment administered in the adjuvant and/or neoadjuvant setting for curative intent
• Patients must have measurable or evaluable disease
• Absolute neutrophil count >= 1500 cells/uL
• Platelets >= 100,000 cells/uL
• Total bilirubin = = 50 mL/min
• Prothrombin time (PT)/partial thromboplastin time (PTT) = = 12 weeks
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately and be discontinued on study; subjects should be instructed to notify the investigator if it is determined after completion of the study that they became pregnant during the treatment phase of the study; the anticipated date or birth or termination of the pregnancy should be provided at the time of the initial report; whenever possible, a pregnancy should be followed to term, any premature terminations reported, and the status of the mother and the child should be reported to the study monitor after delivery; if the outcome of the pregnancy meets any severe adverse events (SAE) classification criterion, the investigator must follow the procedures for reporting SAEs; any neonatal death occurring = = 4 weeks prior to first dose of study drug and the subject must be recovered from the acute toxic effects of the treatment prior to first dose of study drug (defined as a return to baseline or a severity of = = 4 weeks prior to the first dose of study drug; subjects may not be currently receiving dexamethasone

Exclusion Criteria

• Female subjects who are pregnant or nursing
• Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to first dose of study drug or those who have not had adverse events return to baseline severity level or a severity of grade 1 due to agents administered more than 4 weeks prior to first dose of study drug
• Subjects with a history of congestive heart failure (CHF) requiring medical therapy
• Subjects with serum amylase or lipase > 1.5 ULN
• Subjects with previous high dose chemotherapy with autologous stem cell rescue bone marrow transplantation
• History of organ or allogeneic bone marrow transplant
• Use of any investigational agent or device within 4 weeks prior to first dose of study drug
• Metastatic disease to the central nervous system (CNS) requiring treatment or radiation therapy
• Subjects with known untreated brain metastases or treated brain metastases that have not been stable >= 4 weeks prior to first dose of study drug
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (including human immunodeficiency virus [HIV] not stable on antiretroviral therapy), symptomatic congestive heart failure, hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, as determined by the investigator
• History of prior malignancy not cured by excision; patients with non-melanoma skin cancer or carcinoma in situ of the cervix are not excluded, but patients with other prior malignancies must have had at least 2-year disease free interval
• Concurrent therapeutic anticoagulation: PTT less than or equal to 1.5 x ULN or low dose aspirin and low-molecular weight heparin only are allowed; Coumadin will be allowed on a case by case basis if use is chronic and approved by the