Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Rectal Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial Using a Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Patients With Newly Diagnosed Resectable Rectal Cancer|
- Pathologic Complete Response (PCR) [ Time Frame: At surgery (up to 6 weeks after end of treatment) ] [ Designated as safety issue: No ]The pathologic complete response (PCR) rate will be calculated as the proportion of patients who achieve complete response out of all evaluable patients. PCR is defined as the total absence of residual tumor cells by microscopic examination of the resected surgical specimen, including all of the sampled lymph nodes.
- Toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
All toxicities encountered during the study will be evaluated according to the grading system (0-5) NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0.
Toxicity will be reported as the proportion of subjects experiencing Grades 3,4, and 5 adverse events (AEs) out of all evaluable patients
- Progression-free Survival (PFS) [ Time Frame: 3 years after surgery ] [ Designated as safety issue: No ]
The Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (Version 1.0) will be used to determine tumor response and progression. Progressive disease (PD) for target lesions: >= 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered . PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions or unequivocal progression of existing non-target lesions. Time to progression will be measured from the time of surgery or clinically documented down staging if surgery for whatever reason is not carried in the subject until there is evidence of PD.
Progression-free survival is reported as the percentage of patients who have not experienced progression of disease at three years post-surgery
- Incidence of Sphincter-sparing Surgery [ Time Frame: At surgery (up to 6 weeks after end of treatment) ] [ Designated as safety issue: No ]Incidence of sphincter-saving surgery is defined as the proportion of subjects who do not have permanent colostomy at the final follow-up out of all evaluable patients.
- Surgical Downstaging Rate [ Time Frame: At surgery (up to 6 weeks after treatment) ] [ Designated as safety issue: No ]Downstaging rate after neoadjuvant treatment with combination oxaliplatin, capecitabine, celecoxib and concurrent radiation is defined as the proportion of patients whose pathological stage (stage at surgery) is different from their clinical stage (stage at baseline)
- Pelvic Local Control Rate [ Time Frame: Up to 3 years after surgery ] [ Designated as safety issue: No ]Pelvic local control rate is defined as the proportion of subjects who have no evidence of pelvic recurrence (by standard clinical assessment, including CT scan and clinical examination) at the final follow-up evaluation, out of all evaluable patients
|Study Start Date:||April 2005|
|Study Completion Date:||May 2015|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Chemotherapy, Celecoxib, and Radiation
Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation.
Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day [1700 mg/m2/day] (Monday through Friday during radiation therapy).
Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break.
Other: Chemotherapy, Celecoxib, and Radiation
Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Improved regional control as demonstrated by a lower incidence of local recurrence after concurrent chemoradiation delivered either pre-operatively or post-operatively for resectable rectal cancer is supported by clinical trial data but the impact on overall survival with either approach remains controversial. An ideal regimen for preoperative chemoradiation in locally advanced rectal cancer would include agents that are both potent radio-sensitizers and effective in treating micro-metastatic disease without excessive toxicity. The cyclooxygenase-2 (COX-2) enzyme is over expressed in colorectal cancer, but the exact role of this over expression in tumorigenesis remains an active area of research. The area with the most potential in using cyclooxygenase-2 inhibitors in cancer treatment may be to use them as an adjunct to other modalities of treatment.
Taking into consideration all the above, a previous pilot trial of neoadjuvant therapy with combined oxaliplatin, capecitabine, celecoxib (a COX-2 inhibitor), and radiation was conducted in four patients with operable rectal cancer. Promising results, including pain relief and downstaging of cancer, were observed.
Therefore, this single-arm phase II trial of preoperative concurrent chemoradiation for patients with T3-4N0-2M0 rectal cancer was initiated to assess patient outcomes and explore the relationship between COX-2 expression in surgical specimens and therapeutic endpoints.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00250835
|United States, New Mexico|
|Hematology Oncology Associates|
|Albuquerque, New Mexico, United States, 87106|
|University of New Mexico Cancer Center|
|Albuquerque, New Mexico, United States, 87106|
|New Mexico Cancer Care Associates|
|Santa Fe, New Mexico, United States, 87505|
|Principal Investigator:||Fa-Chyi Lee, MD||University of New Mexico|