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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Laura W. Goff, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00514020
First received: August 8, 2007
Last updated: October 30, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Gastric Cancer
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Genetic: gene expression analysis
Genetic: polymorphism analysis
Genetic: protein expression analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacogenomically Selected Treatment for Gastric and Gastroesophageal Junction (GEJ) Tumors: A Phase II Study

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • 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]) [ Time Frame: every 8 weeks to progression ] [ Designated as safety issue: No ]
    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.


Enrollment: 33
Study Start Date: August 2007
Study Completion Date: February 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment 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: polymorphism analysis
Blood collection
Genetic: protein expression analysis
Blood collection
Other: pharmacological study
Blood collection

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514020

Locations
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, United States, 63110
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Study Chair: Laura W. Goff, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Laura W. Goff, MD, Assistant Professor of Medicine; Associate Director, Hematology/Oncology Fellowship Program; Medical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00514020     History of Changes
Other Study ID Numbers: VICC GI 0716, P30CA068485, VU-VICC-GI-0716
Study First Received: August 8, 2007
Results First Received: September 18, 2012
Last Updated: October 30, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
adenocarcinoma of the stomach
stage IV gastric cancer
recurrent gastric cancer

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Oxaliplatin
Fluorouracil
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on September 18, 2014