Back to resultsA Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer
Primary Purpose
Rectal Cancer
Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Capecitabine
Oxaliplatin
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Cancer
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Capecitabine+Oxaliplatin
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Percentage of Participants With Sphincter-preservation
Percentage of participants with sphincter-preservation is reported.
Number of Participants With Marked Laboratory Abnormalities
Number of participants with marked laboratory abnormalities is reported.
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.
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).
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.
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.
Full Information
NCT ID
NCT02694718
First Posted
February 25, 2016
Last Updated
November 21, 2016
Sponsor
Hoffmann-La Roche
Collaborators
Sanofi-Synthélabo (Schweiz) AG
1. Study Identification
Unique Protocol Identification Number
NCT02694718
Brief Title
A Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer
Official Title
A Phase II Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
August 2006 (Actual)
Study Completion Date
November 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
Collaborators
Sanofi-Synthélabo (Schweiz) AG
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to determine the pathological complete tumor response rate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Capecitabine+Oxaliplatin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda, Ro09-1978
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Pathological Complete Tumor Response
Description
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).
Time Frame
Up to Week 16
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sphincter-preservation
Description
Percentage of participants with sphincter-preservation is reported.
Time Frame
Up to Week 16
Title
Number of Participants With Marked Laboratory Abnormalities
Description
Number of participants with marked laboratory abnormalities is reported.
Time Frame
Up to Week 16
Title
Percentage of Participants With Resection (R0) in Participants With T4 Rectal Cancer
Description
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.
Time Frame
Up to Week 16
Title
Percentage of Participants With Downstaging of Primary Tumor and/or Lymph Nodes
Description
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).
Time Frame
From screening to Week 16
Title
Percentage of Participants With Pathological Incomplete Tumor Response
Description
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.
Time Frame
Up to Week 16
Title
Number of Participants With Any Adverse Events and Serious Adverse Events
Description
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.
Time Frame
Up to Week 16
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Chair
Facility Information:
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
City
Luzern
ZIP/Postal Code
6004
Country
Switzerland
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
City
Zürich
ZIP/Postal Code
8037
Country
Switzerland
City
Zürich
ZIP/Postal Code
8063
Country
Switzerland
12. IPD Sharing Statement
Learn more about this trial
A Study of Capecitabine Plus Oxaliplatin in Combination With Pre-operative Pelvic Radiotherapy in Rectal Cancer
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