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

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ClinicalTrials.gov Identifier: NCT02694718
Recruitment Status : Completed
First Posted : February 29, 2016
Results First Posted : November 9, 2016
Last Update Posted : January 11, 2017
Sponsor:
Collaborator:
Sanofi-Synthélabo (Schweiz) AG
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rectal Cancer
Interventions Drug: Capecitabine
Drug: Oxaliplatin
Enrollment 60
Recruitment Details A total of 60 participants were enrolled in this study conducted from 30 March 2005 to 28 November 2006 at 6 centers in Switzerland.
Pre-assignment Details  
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group 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.
Period Title: Overall Study
Started 60
Completed 58
Not Completed 2
Reason Not Completed
Death             1
Withdrawal by Subject             1
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
Safety population included all the participants who received at least one dose of any of the study treatments and who had a baseline assessment.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 60 participants
61
(35 to 77)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
14
  23.3%
Male
46
  76.7%
1.Primary Outcome
Title Percentage of Participants With Pathological Complete Tumor Response
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) population included all participants, who received at least one dose of study drug.
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
23
(13.4 to 36.0)
2.Secondary Outcome
Title Percentage of Participants With Sphincter-preservation
Hide Description Percentage of participants with sphincter-preservation is reported.
Time Frame Up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants, who received at least one dose of study drug. Two participants from the ITT population did not undergo surgery (one died, one withdrew consent).
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 58
Measure Type: Number
Unit of Measure: Percentage of participants
84.48
3.Secondary Outcome
Title Number of Participants With Marked Laboratory Abnormalities
Hide Description Number of participants with marked laboratory abnormalities is reported.
Time Frame Up to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received at least one dose of any of the study treatments and who had a baseline assessment.
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: Participants
Hemoglobin 7
Hematocrit 7
Erythrocytes 16
Leucocytes total 8
Neutrophils 9
Basophils 1
Eosinophils 2
Monocytes 2
Lymphocytes 42
Platelets 13
ASAT/SGOT 2
ALAT/SGPT 10
Serum albumin 3
Total protein 2
Serum creatinine 2
Glucose 13
Sodium 2
Potassium 2
Calcium 2
4.Secondary Outcome
Title Percentage of Participants With Resection (R0) in Participants With T4 Rectal Cancer
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT consists of all included participants, who received at least one dose of study drug. Five participants from ITT population with T4 rectal cancer underwent surgery.
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: Percentage of participants
100
5.Secondary Outcome
Title Percentage of Participants With Downstaging of Primary Tumor and/or Lymph Nodes
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants, who received at least one dose of study drug.
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: Percentage of participants
T stage 47
N stage 48
Overall 65
6.Secondary Outcome
Title Percentage of Participants With Pathological Incomplete Tumor Response
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants, who received at least one dose of study medication.
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
72
(58.6 to 82.5)
7.Secondary Outcome
Title Number of Participants With Any Adverse Events and Serious Adverse Events
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the participants who received at least one dose of any of the study treatments and who had a baseline assessment.
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description:
Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: Participants
Any AEs 59
Any SAEs 8
Time Frame Up to Week 16
Adverse Event Reporting Description 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 SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalisation or prolongation of hospitalisation or results in disability/incapacity, and congenital anomaly/birth defect.
 
Arm/Group Title Capecitabine + Oxaliplatin
Hide Arm/Group Description Eligible participants received capecitabine 1000 mg/m^2 on Days 1-14, and 825 mg/m^2 on Days 22-35 and 43-56 bid orally, along with oxaliplatin as a 2-hour 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 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.
All-Cause Mortality
Capecitabine + Oxaliplatin
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Capecitabine + Oxaliplatin
Affected / at Risk (%)
Total   8/60 (13.33%) 
Gastrointestinal disorders   
Diarrhoea  1  5/60 (8.33%) 
Abdominal Pain  1  1/60 (1.67%) 
Anal Haemorrhage  1  1/60 (1.67%) 
Colitis  1  1/60 (1.67%) 
Proctitis  1  1/60 (1.67%) 
Stomatitis  1  1/60 (1.67%) 
Subileus  1  1/60 (1.67%) 
Infections and infestations   
Sepsis  1  1/60 (1.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Capecitabine + Oxaliplatin
Affected / at Risk (%)
Total   57/60 (95.00%) 
Gastrointestinal disorders   
Diarrhoea  1  42/60 (70.00%) 
Nausea  1  20/60 (33.33%) 
Proctitis  1  14/60 (23.33%) 
Abdominal Pain  1  8/60 (13.33%) 
Vomiting  1  8/60 (13.33%) 
Painful Defaecation  1  7/60 (11.67%) 
Proctalgia  1  7/60 (11.67%) 
Constipation  1  6/60 (10.00%) 
General disorders   
Fatigue  1  27/60 (45.00%) 
Temperature Intorlerance  1  4/60 (6.67%) 
Pain  1  3/60 (5.00%) 
Investigations   
Weight Decrease  1  5/60 (8.33%) 
Metabolism and nutrition disorders   
Anorexia  1  11/60 (18.33%) 
Nervous system disorders   
Neuropathy  1  13/60 (21.67%) 
Paraesthesia  1  10/60 (16.67%) 
Dysgeusia  1  5/60 (8.33%) 
Peripheral Sensory Neropathy  1  5/60 (8.33%) 
Neuropathy Peripheral  1  4/60 (6.67%) 
Renal and urinary disorders   
Pollakiuria  1  12/60 (20.00%) 
Dysuria  1  5/60 (8.33%) 
Nocturia  1  3/60 (5.00%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  5/60 (8.33%) 
Skin and subcutaneous tissue disorders   
Hand and Foot Syndrome  1  6/60 (10.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
Phone: +41 61 6878333
EMail: global.trial_information@roche.com
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02694718     History of Changes
Other Study ID Numbers: ML18280
First Submitted: February 25, 2016
First Posted: February 29, 2016
Results First Submitted: September 21, 2016
Results First Posted: November 9, 2016
Last Update Posted: January 11, 2017