|Phase II||Biomarker/Laboratory analysis, Treatment||Temporarily closed||18 and over||NCI, Other||CDR0000646724|
NCCTG-N0849, N0849, NCT00938470
RATIONALE: Drugs used in chemotherapy, such as docetaxel, oxaliplatin, capecitabine, and fluorouracil, 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 more than one drug (combination 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 randomized phase II trial is studying giving docetaxel together with oxaliplatin, capecitabine, fluorouracil, and radiation therapy to see how well it works compared with giving fluorouracil together with oxaliplatin and radiation therapy in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction.
Further Study Information
- Assess and compare the pathologic complete response rate of sequential docetaxel, oxaliplatin, and capecitabine followed by fluorouracil, oxaliplatin, and radiotherapy versus fluorouracil, oxaliplatin, and radiotherapy alone in patients with potentially resectable advanced adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia.
- Assess the adverse event profile and safety of these regimens in this patient population.
- Assess and compare the overall survival of patients treated with these regimens.
- Assess and compare the disease-free survival between treatment arms.
- Assess and compare the clinical tumor response rate of these proposed regimens when administered before surgery between treatment arms.
- Evaluate the profiles of pharmacogenetic and proteomic marker measures over time, and assess the association of changes in these biomarkers induced by these proposed regimens with pathologic tumor response and other outcomes of interest.
- Evaluate the profiles of FDG PET/CT measures, including standardized uptake values and % injected dose in the tumor volume over time, and assess the correlation of changes in PET measures with pathologic tumor response and other outcomes of interest.
OUTLINE: This is a multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), and disease stage (II vs III/IVA). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1. Patients also receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive fluorouracil* IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy** 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiotherapy, patients undergo surgery.
- Arm II: Patients receive fluorouracil IV continuously on days 1-5 and oxaliplatin IV over 2 hours on days 1, 15, and 29. Patients also undergo radiotherapy and then surgery as in arm I.* NOTE: * Fluorouracil continuous IV infusion begins within 24 hours of radiotherapy and ends within 24 hours of radiotherapy completion.
NOTE: ** Radiotherapy should begin within 2-6 weeks after completion of 2 courses of docetaxel, oxaliplatin, and capecitabine.
Blood samples are collected at baseline and periodically during study for pharmacogenetic (genetic polymorphisms along with drug target pathways) and proteomic markers (microRNA and mRNA expression) studies. Tumor tissue samples from biopsy and surgery are also collected for pharmacogenetic and proteomic markers studies and future correlative studies.
After completion of study therapy, patients are followed up every 3-6 months for 2 years.
- Histologically confirmed locally advanced adenocarcinoma of the esophagus, gastroesophageal (GE) junction, or gastric cardia
- Surgically resectable disease
- T4N0M0 tumors that are potentially resectable allowed
- T1N0M0 or T2N0M0 tumors not allowed
- Nodal involvement:
- Involvement of celiac nodes (stations 15-20) allowed if the primary lesion is mid-thoracic, distal esophagus, or GE junction
- Supraclavicular node involvement allowed with upper thoracic-esophagus primary lesions
- No palpable supraclavicular nodes, biopsy-proven involvement of supraclavicular nodes, or radiographically involved supraclavicular nodes (> 1.5 cm in greatest dimension) for lesions in mid-thoracic, distal thoracic, or GE junction
- No evidence of distant metastases
- ECOG performance status 0-2
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- Creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able to swallow pills
- Willing to return to NCCTG enrolling institution for follow-up
- Willing to provide mandatory tissue and blood samples for research purposes
- Willing to undergo FDG PET/CT scans for mandatory research purposes
- No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Not immunocompromised unless related to the use of corticosteroids
- No known HIV positivity
- No uncontrolled intercurrent illness including, but not limited to, the following conditions:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness and/or social situations that would limit compliance with study requirements
- No uncontrolled diabetes
- No other active malignancy, except for non-melanoma skin cancer or carcinoma in-situ of the cervix, unless curatively treated with no evidence of disease within the past 5 years and not on concurrent specific treatment for cancer other than hormonal therapy
PRIOR CONCURRENT THERAPY:
- No prior radiotherapy to ≥ 30% of the marrow cavity
- No prior or other concurrent treatment for this malignancy
- No concurrent intensity-modulated radiotherapy
Trial Lead Organizations/Sponsors
North Central Cancer Treatment GroupNational Cancer Institute
|Steven R. Alberts||Study Chair|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00938470
ClinicalTrials.gov processed this data on January 15, 2014
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