Vorinostat, Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Upper Gastrointestinal Cancer

• Status: Completed
• Trial end date: 2013-06-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with irinotecan, fluorouracil, and leucovorin in treating patients with advanced upper gastrointestinal cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Roswell Park Cancer Institute
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Calcium; Camptothecin; Fluorouracil; Irinotecan; Leucovorin; Levoleucovorin; Vorinostat

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed upper gastrointestinal tract cancer, including any of the following:

• Esophageal cancer (adenocarcinoma or squamous cell carcinoma)

• Gastric cancer (adenocarcinoma or squamous cell carcinoma)

• Hepatocellular carcinoma

• Locally advanced, inoperable disease or metastatic disease

• No uncontrolled brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 (Karnofsky PS ≥ 70%)

• Life expectancy > 12 weeks

• Platelet count ≥ 100,000/mcL

• Absolute neutrophil count ≥ 1,500/mcL

• Leukocytes ≥ 3,000/mcL

• Total bilirubin ≤ 1.5 mg/dL

• AST and ALT ≤ 2.5 times upper limit of normal

• Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Able to understand and willing to sign a written informed consent document

• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in the study

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Uncontrolled hypertension

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness/social situations that would limit compliance with study requirements

• No coagulopathy or bleeding disorder

• No known UGT1A1 polymorphism

PRIOR CONCURRENT THERAPY:

• No more than 1 prior chemotherapy for metastatic disease

• No prior histone deacetylase inhibitors

• No concurrent prophylactic hematologic growth factors

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent valproic acid

• No other concurrent investigational therapy

• Concurrent therapeutic anticoagulation therapy is allowed