Fluorouracil, Oxaliplatin, and Leucovorin in Treating Patients With Metastatic Stomach Cancer or Gastroesophageal Junction Cancer

Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal Junction (GEJ) Tumors: A Phase II Study

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, 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 more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving fluorouracil together with oxaliplatin and leucovorin works in treating patients with metastatic stomach cancer or gastroesophageal junction cancer.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Genetic: polymorphism analysis; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Genetic: gene expression analysis; Genetic: protein expression analysis; Other: pharmacological study

Detailed Description

OBJECTIVES:

Primary

• Compare the response rate in patients with "good risk" genotype (TSER*2/*2 or TSER*2/*3 genotype [low TS expression]) to historical control response rates in non-genotype selected patients.

OUTLINE: This is a multicenter study.

Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.

Available tumor tissue samples are assessed for expression of TS at the mRNA and protein levels. The results are correlated with germline and tumor TSER genotypes as well as response to the study treatment regimen. Polymorphisms in other genes associated with treatment outcome or toxicity are also assessed.

After completion of study treatment, patients are followed periodically for 4 years.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37064
      • Vanderbilt-Ingram Cancer Center - Cool Springs
    • Nashville, Tennessee, United States, 37064
      • Vanderbilt-Ingram Cancer Center at Franklin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction

  • Metastatic disease
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan

• No known active brain metastases

  • Patients with treated brain metastases are eligible if stable off steroids for at least 30 days

PATIENT CHARACTERISTICS:

• ECOG performance status ≤ 2 (Karnofsky performance status ≥ 60%)
• Life expectancy ≥ 3 months
• WBC ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• AST or ALT ≤ 2.5 x ULN (< 5 x ULN if known liver metastases)
• Creatinine clearance ≤ 1.5 x ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 21 days after completion of study treatment
• No history of allergic reactions to fluorouracil or oxaliplatin
• No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• No prior therapy for metastatic disease

  • Prior neoadjuvant or adjuvant therapy is allowed if the disease-free interval has been longer than 6 months
• No other concurrent chemotherapy
• No concurrent combination anti-retroviral therapy for HIV-positive patients
• No concurrent routine prophylaxis with filgrastim (G-CSF)
• No other concurrent antineoplastic agents, including chemotherapy, radiation therapy, or biologic agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment

Genetic: polymorphism analysis; Blood collection; Drug: fluorouracil; Given through a vein over 5 minutes and then continuously over 46 hours on days 1 and 15.; Drug: leucovorin calcium; through a vein over 2 hours on days 1 and 15.; Drug: oxaliplatin; 500 ml D5W through a vein over 2 hours on days 1 and 15.; Genetic: gene expression analysis; Blood collection; Genetic: protein expression analysis; Blood collection; Other: pharmacological study; Blood collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Each Response in "Good Risk" Genotype (Thymidylate Synthase Promoter Enhancer Region [TSER]*2/*2 or TSER*2/*3 Genotype [Low TS Expression])	Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. This is a one-time assessment.	every 8 weeks to progression

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Laura W. Goff, MD, Vanderbilt-Ingram Cancer Center

Publications and helpful links

Helpful Links

• Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: August 8, 2007
• First Submitted That Met QC Criteria: August 8, 2007
• First Posted (Estimate): August 9, 2007

Study Record Updates

• Last Update Posted (Estimate): November 1, 2012
• Last Update Submitted That Met QC Criteria: October 30, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: stage IV gastric cancer; recurrent gastric cancer; adenocarcinoma of the stomach
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: VICC GI 0716; P30CA068485 (U.S. NIH Grant/Contract); VU-VICC-GI-0716