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

Gastric Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514020
• Other study ID #: VICC GI 0716
• Secondary ID: P30CA068485VU-VI
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2007
• Last updated: October 30, 2012
• Start date: August 2007
• Est. completion date: February 2011

Study information

• Verified date: October 2012
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: February 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• fluorouracil
Given through a vein over 5 minutes and then continuously over 46 hours on days 1 and 15.
• leucovorin calcium
through a vein over 2 hours on days 1 and 15.
• oxaliplatin
500 ml D5W through a vein over 2 hours on days 1 and 15.

Genetic:
• gene expression analysis
Blood collection
• polymorphism analysis
Blood collection
• protein expression analysis
Blood collection

Other:
• pharmacological study
Blood collection

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center - Cool Springs	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center at Franklin	Nashville	Tennessee
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	St Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No

External Links

•   Vanderbilt-Ingram Cancer Center, Find a Clinical Trial