Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery
Condition: Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Recurrence
Intervention: cyclodextrin-based polymer-camptothecin CRLX101; Laboratory biomarker analysis; Pharmacological studies
Intervention description: Given IV; Correlative studies; Correlative studies
Intervention MeSH terms: Camptothecin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot clinical trial studies cyclodextrin-based nanopharmaceutical CRLX101 in treating
      patients with advanced or metastatic stomach, gastroesophageal, or esophageal cancer that has
      progressed through at least one prior regimen of chemotherapy and cannot be removed by
      surgery. CRLX101 delivers the cytotoxic topoisomerase-1 inhibitor camptothecin into tumor
      cells and is hypothesized to interrupt the growth of tumor cells.
    

Eligibility criteria:

        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 =< 1.5 times the upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN

          -  AST/ALT =< 5 x ULN if liver metastasis is present

          -  Serum creatinine =< 1.5 mg/dL or a measured creatinine clearance >= 50 mL/min

          -  Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x ULN

          -  Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Subjects with a life expectancy >= 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 =< 30 days after birth
             must also be reported as a SAE

          -  Subjects must have an electrocardiogram without evidence of clinically significant
             conduction abnormalities or active ischemia as determined by the investigator and an
             acceptable QTc interval

          -  All subjects must have the ability to understand and the willingness to sign a written
             informed consent

          -  Subjects must not have received prior chemotherapy or radiation within < 4 weeks prior
             to first dose of study drug

          -  Subjects may be entered if they have received prior radiation therapy involving =< 30%
             of the bone marrow; any prior radiation therapy must have been administered >= 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 =< grade 1)

          -  Subjects may be enrolled with a history of treated brain metastases that are
             clinically stable for >= 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 study medical
             monitors

          -  Any major surgery =< 4 week prior to first dose of study drug

          -  Concurrent use of filgrastim (G-CSF) or growth factors at the time of initiation of
             study drug

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to CRLX101 and camptothecins

          -  Subjects with marked baseline prolongation of QT/QTc interval (for females QTc
             interval >= 470 msec and for males QTc interval >= 450 msec)

          -  Subjects, who in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study