A Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer
- Registration Number
- NCT02694718
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this study is to determine the pathological complete tumor response rate.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Capecitabine+Oxaliplatin Capecitabine 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. Capecitabine+Oxaliplatin Oxaliplatin 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Pathological Complete Tumor Response Up to Week 16 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).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Downstaging of Primary Tumor and/or Lymph Nodes From screening to Week 16 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).
Percentage of Participants With Pathological Incomplete Tumor Response Up to Week 16 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.
Number of Participants With Any Adverse Events and Serious Adverse Events Up to Week 16 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.
Percentage of Participants With Resection (R0) in Participants With T4 Rectal Cancer Up to Week 16 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.
Percentage of Participants With Sphincter-preservation Up to Week 16 Percentage of participants with sphincter-preservation is reported.
Number of Participants With Marked Laboratory Abnormalities Up to Week 16 Number of participants with marked laboratory abnormalities is reported.