Clinical Trial Result Information
Protocol number
ML18280
Title of Study
A Phase II Study of Capecitabine plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer.
Sponsor
Roche Pharma (Schweiz) AG; Co-Sponsor Sanofi-Synthélabo (Schweiz) AG
Company division
Pharmaceutical
Product name
Xeloda
Generic name
capecitabine
Therapeutic area
Colorectal Cancer
Clinical study summary
This was a prospective, open-label, one-arm, multicenter national phase II study in patients with rectal cancer, investigating treatment consisting of one cycle of neoadjuvant XELOX (capecitabine + oxaliplatin) followed by 5 weeks of preoperative radiotherapy combined with capecitabine + oxaliplatin.
Study center(s)
6 centers in Switzerland
Phase of development
II
Objectives
Primary: To determine the pathological complete tumor response rate.
Secondary: To determine the sphincter-preservation rate; to determine the rate of R0 resection in patients with T4 rectal cancer; to assess the downstaging rate of primary tumor and/or lymph nodes; to assess the pathological incomplete tumor response rate (= Grade 1 or 2 histological grading of regression according to Dworak regression grading classification); to evaluate the safety profile of the treatment.
Methodology
Eligible patients received one cycle of neoadjuvant XELOX (capecitabine + oxliplatin) followed by 5 weeks of preoperative radiotherapy combined with capecitabine + oxaliplatin.
During the treatment period vital signs, ECOG performance status and hematology were performed at every visit. Blood chemistry was performed on Days 22 and 43.
During the surgery period (Day 85 to Day 113) vital signs, ECOG performance status, colonoscopy, CEA, hematology, blood chemistry and pathology were performed.
Safety was assessed through the recording of adverse events, concomitant medications and clinical laboratory tests.
Number of patients (planned/analyzed)
60 enrolled
Diagnosis and main criteria for inclusion
Adult patients >=18 years of age with histologically proven locally advanced T3/T4 rectal carcinoma with or without nodal involvement requiring surgery of the primary tumor.
Test product, dose and mode of administration or test procedure
Xeloda (capecitabine) orally at a dose of 1000mg/m2 bid on days 1-14 and at a dosage of 825mg/m2 bid on days 22-35 and 43-56.
Oxaliplatin as a 2-hour intravenous infusion of 130mg/m2/d on day 1 and 50mg/m2/d on days 22, 29, 43 and 50 prior to radiotherapy.
Duration of treatment
8 weeks
Reference therapy, dose and mode of administration or reference procedure
N/A.
Criteria for evaluation (efficacy, safety)
Efficacy: Pathological complete response rate defined as Dworak grade 3 or 4.
Secondary: Sphincter-preservation; R0 resection in patients with T4 rectal cancer; downstaging of primary tumor and/or lymph nodes, defined as decrease by = 1 point(s) in T-value and/or N-value, resepctively; pathological incomplete tumor response rate (=Grade 1 or 2 in Dworak regression grading classification).
Safety: AEs and lab values according to NCI CTCAE (version 3.0).
Statistical methods
Descriptive statistics were used for summarization and analysis of efficacy parameters.
Summary (efficacy, safety, other results)
Efficacy: A pathological complete tumor response defined as Dworak grade 3 or 4 was assessed for 14 patients (23%). Using the Pearson-Clopper method a 95%-CI of [13.4%, 36.0%] was calculated for pathological complete tumor response rate.
According to the Dworak classification, seven patients (12%) were classed as grade 4, seven (12%) as grade 3, 23 (40%) as grade 1 and 1 (2%) as grade 0. Two patients were unevaluable since they did not undergo surgery.
Sphincter-preservation was reported for 49 patients (84%).
Six patients recorded T4 rectal cancer in the cTNM assessment at the screening visit. Five of these patients had surgery at visit 13. For all patients with T4 rectal cancer who received surgery R0 resection was reported in the pathological assessment at visit 14.
Comparing the cTNM assessment at screening and the ypTNM assessment at visit 14, a downgrading of the primary tumor and/or lymph nodes in T-stage and/or N-stage was reported for 39 patients (65%). Downgrading of T-stage was assessed in 32 patients (53%) and downgrading of N-stage was assessed in 31 patients (52%). An upstaging of primary tumor in T-stage and/or N-stage was reported for 13 patients (22%).
All efficacy analyses were repeated on the per-protocol population. Results were comparable to the results on the ITT population.
Safety: During the study the most frequently reported adverse event was diarrhea (70%), followed by fatigue (45%), nausea (33%), proctitis (23%), neuropathy (22%), pollakiuria (20%), anorexia (18%), paraesthesia (17%), abdominal pain (13%), vomiting (13%), painful defecation (12%), proctalgia (12%), constipation (10%) and palmar-plantar erythrodysesthesia syndrome (10%). Eight patients experienced serious adverse events. One patient died after the first cycle of chemotherapy, due to sepsis.
Conclusions
Preoperative Xeloda + oxaliplatin (XELOX) in combination with pre-operative pelvic radiation was shown to be a feasible treatment regimen, resulting in encouragingly high rates of pathological complete response, R0 resection, sphincter preservation, and tumor downstaging in patients with locally advanced rectal cancer.
Publications (references, if available)
Koeberle D, Burkhard R, von Moos R at al. Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer. Br. J. Cancer. Advance online publication. 18th March 2008
Date of report
9/3/2007
Click here for the protocol registry listing of this trial.
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