A Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the pathological complete tumor response rate.

Official Title
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A Phase II Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed locally advanced T3/T4 rectal carcinoma with or without nodal involvement requiring surgery of the primary tumor Eastern Cooperative Oncology Group performance status 0-2 Adequate values of laboratory parameters Exclusion Criteria: Evidence of distant metastases Previous Chemotherapy or immunotherapy for colorectal cancer Previous radiotherapy to the pelvis Pre-existing condition which would deter radiotherapy Malignancy within last 5 years, except cured basal cell cancer of the skin and in situ cancer of the cervix Clinically significant cardiac disease or myocardial infarction within the last 12 months Lack of physical integrity of the upper gastrointestinal tract or those who have malabsorption syndrome Organ allografts Concomitant treatment with brivudine, lamivudine, ribavirin or any other nucleoside analogues Dihydropyrimidine dehydrogenase (DPD) deficiency History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capecitabine+Oxaliplatin<br>Eligible participants received capecitabine 1000 milligrams per square meter (mg/m^2) on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 twice a day (bid) orally, along with oxaliplatin as a 2-hour intravenous (iv) infusion of 130 mg/m^2/once a day (d) on Day 1 and 50 mg/m^2/d on Days 22, 29, 43 and 50 prior to radiotherapy. Participants received radiation therapy having a fraction dose of 1.8 gray (Gy)/day, 5 days a week, for five consecutive weeks starting on Day 22 of the treatment period. Participants, who completed the treatment period, underwent surgery at Week 14. | Drug: Capecitabine<br>* Capecitabine is available as 50 mg and 500 mg tablets. It will be administered as a 1000mg/m^2 bid orally on Days 1-14, and at a dose of 825mg/m^2 bid on Days 22-35 and 43-56.<br>* Other names: Xeloda, Ro09-1978;Drug: Oxaliplatin<br>* Oxaliplatin is available in vials containing 50 mg or 100 mg. It will be administered as a oxaliplatin 130mg/m^2/d intravenously on Day 1 and 50mg/m^2/d on Days 22, 29, 43 and 50 prior to radiotherapy up to Week 9 followed by surgery period.<br>* Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Pathological Complete Tumor Response | Pathological complete tumor response was defined as grade 3 or 4 in the histological grading of regression according to Dworak classification. Grade 0 is no regression; Grade 1 is dominant tumor mass with obvious fibrosis and/or vasculopathy; Grade 2 is dominantly fibrotic changes with few tumor cells or groups; Grade 3 is defined as very few (difficult to find microscopically) tumor cells in fibrotic tissue with or without mucous substance; Grade 4 is defined as no tumor cells, only fibrotic mass (total regression or response). | Up to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sphincter-preservation | Percentage of participants with sphincter-preservation is reported. | Up to Week 16 | 
| Number of Participants With Marked Laboratory Abnormalities | Number of participants with marked laboratory abnormalities is reported. | Up to Week 16 | 
| Percentage of Participants With Resection (R0) in Participants With T4 Rectal Cancer | R0 resection was defined as complete resection of the tumor with adequate tumor-free margins and regional lymph node extirpation as confirmed by pathology after pre-operative chemotherapy plus capecitabine + oxaliplatin therapy. | Up to Week 16 | 
| Percentage of Participants With Downstaging of Primary Tumor and/or Lymph Nodes | Downstaging of primary tumor (T) and/or lymph nodes (N) was defined as decrease by 1 point in T-value and/or N-value (comparing at screening and after treatment). It was assessed by colonoscopy, pathology, endosonography of rectum, chest X-ray, abdominopelvic Computed Tomography and Magnetic Resonance Imaging. Staging for tumor are: TX (primary tumor cannot be assessed), T0 (no evidence of primary tumor), Tis (carcinoma in situ), T1 (tumor invades submucosa), T2 (tumor invades muscularis propria), T3 (tumor invades through muscularis propria into subserosa/into non-peritonealized pericolic/perirectal tissues, T4 (tumor directly invades other organs or structures). Staging for lymph nodes are: NX (regional lymph nodes cannot be assessed), N0 (no regional lymph node metastasis), N1 (metastasis in 1 to 3 regional lymph nodes), N2 (metastasis in 4 or more regional lymph nodes). | From screening to Week 16 | 
| Percentage of Participants With Pathological Incomplete Tumor Response | Pathological incomplete tumor response was defined as grade 1 or 2 in the histological grading of regression according to Dworak grading of regression. Pathological incomplete tumor response rate, Grade 1: dominant tumor mass with obvious fibrosis and/or vasculopathy; Grade 2: dominantly fibrotic changes with few tumor cells or groups (easy to find) were assessed. | Up to Week 16 | 
| Number of Participants With Any Adverse Events and Serious Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in participants or clinical investigation participants administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. | Up to Week 16 |