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

NCT00537121 | Completed Phase 1 DMC

• 2 other identifiers: CDR0000564857RPCI-I-78806
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Esophageal Cancer; Gastric Cancer; Liver Cancer

Keywords

recurrent gastric cancer; stage IV gastric cancer; recurrent esophageal cancer; stage IV esophageal cancer; adenocarcinoma of the esophagus; adenocarcinoma of the stomach; squamous cell carcinoma of the esophagus; adult primary hepatocellular carcinoma; stage III gastric cancer; stage III esophageal cancer; advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of vorinostat (SAHA) when administered continuously and intermittently with standard doses of irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI)

  4 weeks

• Recommended phase II dose (RPTD) of SAHA when administered continuously and intermittently with standard doses of FOLFIRI

  4 weeks

Secondary Outcomes (5)

• Toxicity of the SAHA and FOLFIRI combination

  Baseline and after 2 weeks of Treatment

• Effects of SAHA and FOLFIRI combination on TGF-β signaling and survivin expression

  Every 6 months

• Response rate

  Every 6 months

• Progression-free survival

  Every 6 months

• Overall survival

  Every 3 months for 5 years

Interventions

fluorouracil DRUG

Given IV

irinotecan hydrochloride DRUG

Given IV

leucovorin calcium DRUG

Given IV

vorinostat DRUG

Taken Orally

pharmacological study OTHER

Correlative Study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Liver Neoplasms; Adenocarcinoma Of Esophagus; Esophageal Squamous Cell Carcinoma; Carcinoma, Hepatocellular

Interventions

Fluorouracil; Irinotecan; Leucovorin; Vorinostat

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Liver Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Adenocarcinoma

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Nikhil Khushalani, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2007
• First Posted: September 28, 2007
• Study Start: November 1, 2006
• Primary Completion: October 1, 2012
• Study Completion: June 1, 2013
• Last Updated: June 28, 2013

Record last verified: 2013-06

Locations

US (1)