Gastric Cancer
Conditions
Keywords
adenocarcinoma of the stomach, stage IV gastric cancer, recurrent gastric cancer
Brief 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.
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.
Interventions
DRUGfluorouracil
Given through a vein over 5 minutes and then continuously over 46 hours on days 1 and 15.
DRUGleucovorin calcium
through a vein over 2 hours on days 1 and 15.
DRUGoxaliplatin
500 ml D5W through a vein over 2 hours on days 1 and 15.
GENETICgene expression analysis
Blood collection
GENETICpolymorphism analysis
Blood collection
GENETICprotein expression analysis
Blood collection
OTHERpharmacological study
Blood collection
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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]) | every 8 weeks to progression | 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted from August 2007 to March 2011.
Pre-assignment details
Forty-two patients signed consent, 9 of which were found to be ineligible to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Oxaliplatin + Leucovorin + 5-Fluorouracil Patients receive oxaliplatin IV over 2 hours, leucovorin calcium intravenously (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. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | disease progression | 9 |
| Overall Study | other complicating disease | 2 |
| Overall Study | patients moved to the no tx group | 6 |
| Overall Study | patient went to radiation treatment | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Oxaliplatin + Leucovorin + 5-Fluorouracil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age Continuous | 58 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 14 / 24 |
Outcome results
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.
Time frame: every 8 weeks to progression
Population: Patients available for measurement of response. All patients who received Oxaliplatin + Leucovorin + 5-Fluorouracil are in the heterozygous good risk genotype group. One patient was not evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxaliplatin + Leucovorin + 5-Fluorouracil | 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]) | Complete Response | 0 participants |
| Oxaliplatin + Leucovorin + 5-Fluorouracil | 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]) | Partial Response | 9 participants |
| Oxaliplatin + Leucovorin + 5-Fluorouracil | 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]) | Progressive Disease | 1 participants |
| Oxaliplatin + Leucovorin + 5-Fluorouracil | 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]) | Stable Disease | 14 participants |