Esophageal Cancer
Conditions
Keywords
adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal 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. 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 undergoing surgery for stage II, stage III, or stage IV esophageal cancer.
Detailed description
OBJECTIVES: Primary * Determine the complete pathologic response (complete response \[CR\]) rate in patients with stage II-IVA esophageal cancer treated with neoadjuvant oxaliplatin, capecitabine, and radiotherapy. Secondary * Determine the clinical efficacy and toxicity of this regimen in these patients. * Determine the quality of life of patients treated with this regimen. * Identify basal expression and changes in gene expression that relate to CR, relapse, and survival of patients treated with this regimen. OUTLINE: * Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 (weeks 1, 3, and 5). Patients also undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38 and receive oral or enteral capecitabine twice daily on the same days they undergo radiotherapy. * Surgery: At 4-6 weeks after completion of neoadjuvant chemoradiotherapy, patients who are eligible undergo esophagectomy. * Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and oral or enteral capecitabine twice daily on days 1-5, 8-12, 15-19, 22-26, and 29. Treatment repeats approximately every 14 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsies periodically. Collected samples are analyzed by gene expression studies, microarray analysis, and real-time quantitative reverse transcriptase-PCR to identify basal expression and changes in gene expression. Quality of life is assessed periodically. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.
Interventions
DRUGcapecitabine
Oral
DRUGoxaliplatin
IV
GENETICgene expression analysis
Correlative Study
GENETICmicroarray analysis
Correlative Study
GENETICreverse transcriptase-polymerase chain reaction
Correlative Study
PROCEDUREadjuvant therapy
Metastatic growth control
PROCEDUREbiopsy
Examination of tissue type
PROCEDUREconventional surgery
Tissue removal
PROCEDUREneoadjuvant therapy
Tumor shrinkage
PROCEDUREquality-of-life assessment
Correlative Study
RADIATIONradiation therapy
Undergoing radiation therapy
Sponsors
National Comprehensive Cancer Network
Roswell Park Cancer Institute
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: * Diagnosis of squamous cell carcinoma of the esophagus or adenocarcinoma of the esophagus * Stage II-IVA disease as determined by clinical staging, including endoscopy and CT scan with or without endoscopic ultrasound * Bulk of gastroesophageal junction tumor should be in the esophagus * Bronchoscopy with biopsy and cytology required if primary esophageal cancer is \< 26 cm from incisors * No known brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy \> 4 months * WBC \> 4,000/mm³ * ANC \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Hemoglobin \> 9 g/dL * Bilirubin normal * Creatinine normal * AST \< 2.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * Able to take oral medication or undergo enteral administration of medication * No peripheral neuropathy ≥ grade 2 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 90 days after completion of study treatment * No hypersensitivity to platinum compounds, fluoropyrimidines, or antiemetics administered in combination with protocol-directed chemotherapy * No concurrent uncontrolled illness, including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situation that would preclude study compliance * No history of second malignancy except for curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer * Other cured tumors allowed at discretion of the principal investigator * No known HIV or hepatitis B or C (active and/or previously treated) PRIOR CONCURRENT THERAPY: * No prior therapy for esophageal cancer * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Response | 5.5 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (Complete and Partial Response) as Measured by RECIST Criteria After Course 1 | 5.5 weeks |
| Median Time to Progression | 5.5 weeks |
| Quality of Life Improved Rate | 5.5 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COR(Capecitabine in Combination w/Oxaliplatin and Radiotherapy Cycle 1:
Oxaliplatin (Oxa) 85 mg/m2 IV on days (D) 1, 15 29. Capecitabine (Cap) 1250 mg/m2 in 2 divided daily doses P0 or enteral tube on radiation days (Monday- Friday/weekly), and continued until final dose of radiotherapy. Radiation administered as 1.8 Gy in 28 fractions starting on day 1. Four to six weeks after completion of Cycle I chemoradiotherapy, eligible patients will undergo esophagectomy. Cycles 2 and 3: Postoperatively, in the absence of progression, patients will be eligible for cycles 2 and 3. Cycle 2 will commence at minimum 4 to 6 weeks post-operatively, but no later than 12 weeks post-operatively. Cycles 2 and 3 will consist of OXA and CAP in the same dosage as that last administered during cycle 1. During cycles 2 and 3, CAP will be administered on days 1-29 (Monday- Friday/ weekly) and oxaliplatin on days 1, 15, 29. A minimum of 2 weeks is recommended between cycles 2 and 3. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | disease Progression | 4 |
| Overall Study | Not Treated(became ineligible) | 4 |
| Overall Study | Not treated (other) | 1 |
| Overall Study | other | 5 |
| Overall Study | recurrence | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | COR(Capecitabine in Combination w/Oxaliplatin and Radiotherapy |
|---|---|
| Age Continuous | 59.53 years STANDARD_DEVIATION 10.06 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 12 / 36 |
Outcome results
Primary
Complete Response
Time frame: 5.5 weeks
Population: Evaluable Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COR(Capecitabine in Combination w/Oxaliplatin and Radiotherapy | Complete Response | 27.78 percentage of patients |
Secondary
Median Time to Progression
Time frame: 5.5 weeks
Population: Evaluable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COR(Capecitabine in Combination w/Oxaliplatin and Radiotherapy | Median Time to Progression | NA months |
Secondary
Overall Response Rate (Complete and Partial Response) as Measured by RECIST Criteria After Course 1
Time frame: 5.5 weeks
Population: evaluable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COR(Capecitabine in Combination w/Oxaliplatin and Radiotherapy | Overall Response Rate (Complete and Partial Response) as Measured by RECIST Criteria After Course 1 | 58.33 percentage of patients |
Secondary
Quality of Life Improved Rate
Time frame: 5.5 weeks
Population: evaluable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COR(Capecitabine in Combination w/Oxaliplatin and Radiotherapy | Quality of Life Improved Rate | 66.67 percentage of patients |