Gastric Cancer
Conditions
Keywords
adenocarcinoma of the stomach, stage I gastric cancer, stage II gastric cancer, stage III gastric cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with radiation therapy works in treating patients with stomach cancer that can be removed by surgery.
Detailed description
OBJECTIVES: * Determine the pathologic complete response rate in patients with primary gastric adenocarcinoma treated with neoadjuvant chemoradiotherapy comprising oxaliplatin, capecitabine, and radiotherapy. (This will not be completed as this study was closed early due to poor accrual.) * Assess the frequency and severity of toxicities associated with this regimen. * Explore, preliminarily, the association between DNA repair genes (ERCC-1, XRCC1, GST-P1, XPD, XPA, ribonucleotide reductase), target enzymes (thymidylate synthase \[TS\], dihydropyrimidine dehydrogenase, thymidine phosphorylase \[TP\]), and angiogenic factors (vascular endothelial growth factor \[VEGF\], epidermal growth factor \[EGF\], PD-ECGF, basic fibroblast growth factor, TSP-1 and -2, transforming growth factor \[TGF\]-β, and IL-8) and response to neoadjuvant therapy in patients with adenocarcinoma of the stomach. (This will not be completed as this study was closed early due to poor accrual.) * Explore, preliminarily, the association of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response and toxicity to neoadjuvant chemoradiation therapy in these patients. (This will not be completed as this study was closed early due to poor accrual.) * Explore, preliminarily, the feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response to neoadjuvant chemoradiation therapy. (This will not be completed as this study was closed early due to poor accrual.) OUTLINE: This is a multicenter, pilot study. * Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1 and 22 and oral capecitabine twice daily on days 1-14 and 22-35 in the absence of disease progression or unacceptable toxicity. * Neoadjuvant chemoradiotherapy: Patients receive oral capecitabine twice daily on days 43-77 and undergo radiotherapy once daily on days 43-47, 50-54, 57-61, 64-68, and 71-75 in the absence of disease progression or unacceptable toxicity. * Surgery: Patients with stable or responding disease undergo surgery 4-6 weeks after completion of chemoradiotherapy. Tumor tissue is obtained at surgery or endoscopic biopsy. Gene expression analysis and comparative genomic hybridization testing are conducted on the tissue. Blood is drawn prior to beginning study treatment and is analyzed for germline polymorphisms. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.
Interventions
DRUGcapecitabine
850 mg/m2/dose PO q 12 hours Days 1-14 and 22-35. 650 mg/m2/dose PO q 12 hours Days 43-77.
DRUGoxaliplatin
130 mg/m2 by 2-hour infusion Days 1 and 22
PROCEDUREconventional surgery
Distal subtotal gastrectomy, total gastrectomy, or proximal gastrectomy
RADIATIONradiation therapy
Beginning Day 43, patients will be treated 5 days/week at 180 cGy/day times 25 fractions to a total dose of 4,500 cGy.
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary adenocarcinoma of the stomach, meeting the following criteria: * Newly diagnosed disease amenable to curative resection * Stage IB-III (T2-4) * Measurable or nonmeasurable disease * Enlarged lymph nodes outside of radiation fields must have preoperative biopsies * No positive lymph nodes outside of radiation fields * No distant metastasis * No gastroesophageal junction tumors PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Absolute neutrophil count ≥ 1,500/mm³ * WBC ≥ 3,000/mm³ * Platelet count ≥ 100,000/mm³ * Creatinine ≤ 1.5 times upper limit of normal * Albumin ≥ 3 g/dL * Bilirubin normal * No evidence of ischemic heart disease by EKG * No coronary artery disease requiring active medical treatment * No symptoms of angina * No history of myocardial infarction * No deep vein thrombosis within the past 12 months * No pre-existing peripheral neuropathy * No active pneumonia or inflammatory lung infiltrate * No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for ≥ 5 years * No clinically significant comorbid medical conditions that would prevent delivery of chemotherapy, radiotherapy, or the performance of surgery * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior and no concurrent sorivudine or brivudine * No prior therapy for this malignancy, including chemotherapy, surgery, immunotherapy, or radiotherapy * No prior coronary angioplasty or stenting * No concurrent 2-dimensional or intensity-modulated radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response | 17-19 weeks | Pathologic complete response rates (pCR) of primary gastric adenocarcinoma when treated with oxaliplatin and capecitabine followed by capecitabine and radiation pre-operatively. On review of the resected gastric specimen and accompanying lymph nodes, pCR is no cancer recognized by the pathologist. Margins are free of tumor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Patients were assessed for adverse events after pre-operative chemotherapy, after pre-operative chemoradiation and within 14 days of surgery. | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy, Chemoradiation, Surgery Oxaliplatin 130 mg/m2 (2 hour IV infusion on Days 1 and 22), Capecitabine 850 mg/m2/dose (PO q 12 hours on Days 1-14 and 22-35), Capecitabine 650 mg/m2/dose (PO q 12 hours on days 43-77), Radiation therapy 180 cGy/day, 5 days/week beginning on Day 43. Patients with stable disease or better were to have distal subtotal gastrectomy, total gastrectomy, or proximal gastrectomy. | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Ineligible | 1 |
Baseline characteristics
| Characteristic | Chemotherapy, Chemoradiation, Surgery |
|---|---|
| Age Continuous | 72 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Pathologic Complete Response
Pathologic complete response rates (pCR) of primary gastric adenocarcinoma when treated with oxaliplatin and capecitabine followed by capecitabine and radiation pre-operatively. On review of the resected gastric specimen and accompanying lymph nodes, pCR is no cancer recognized by the pathologist. Margins are free of tumor.
Time frame: 17-19 weeks
Population: Eligible patients who completed pre-operative therapy were assessed for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy, Chemoradiation and Surgery | Pathologic Complete Response | Unconfirmed Partial Response | 2 participants |
| Chemotherapy, Chemoradiation and Surgery | Pathologic Complete Response | Stable/No Response | 2 participants |
| Chemotherapy, Chemoradiation and Surgery | Pathologic Complete Response | Increasing Disease | 1 participants |
| Chemotherapy, Chemoradiation and Surgery | Pathologic Complete Response | Unconfirmed Complete Response | 1 participants |
| Chemotherapy, Chemoradiation and Surgery | Pathologic Complete Response | Assessment Inadequate | 1 participants |
Secondary
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal.
Time frame: Patients were assessed for adverse events after pre-operative chemotherapy, after pre-operative chemoradiation and within 14 days of surgery.
Population: Eligible patients who received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Anorexia | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dehydration | 2 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 2 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Gastrointestinal-Other (Specify) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 2 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Nausea | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Necrosis, GI - Small bowel NOS | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Phosphate, serum-low (hypophosphatemia) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Platelets | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Potassium, serum-low (hypokalemia) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-low (hyponatremia) | 1 Participants with a given type of AE |
| Chemotherapy, Chemoradiation and Surgery | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Vomiting | 1 Participants with a given type of AE |