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An Observational Study of First-Line Capecitabine Based Chemotherapy in Participants With Metastatic Colorectal Cancer (AXEL)

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ClinicalTrials.gov Identifier: NCT01696695
Recruitment Status : Completed
First Posted : October 1, 2012
Results First Posted : November 9, 2016
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Colorectal Cancer
Interventions Drug: Capecitabine
Drug: Chemotherapy
Enrollment 882
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Metastatic Colorectal Carcinoma (mCRC) Participants
Hide Arm/Group Description Newly diagnosed metastatic colorectal carcinoma (mCRC) participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Period Title: Overall Study
Started 882
Completed 0
Not Completed 882
Reason Not Completed
Disease progression             373
Death             29
Adverse Event             74
Withdrawal by Subject             92
Lost to Follow-up             48
Other             74
Major Protocol Violation             192
Arm/Group Title mCRC Participants
Hide Arm/Group Description Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Baseline Participants 690
Hide Baseline Analysis Population Description
Intent to treat (ITT) population included all enrolled participants who provided evaluable data for efficacy variables.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 690 participants
64.9  (10.51)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 690 participants
Female
289
  41.9%
Male
401
  58.1%
1.Primary Outcome
Title Median Progression-free Survival (PFS)
Hide Description PFS was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and is defined as the time from the first dose of indicated treatment to disease progression (PD) or death, whichever occurred first. Participants who did not progress or died while being followed were censored on the date of the last visit. Participants without post-baseline tumor assessments were conservatively censored on the date of first study medication, which is PFS was assigned a value of 1 day. PD: at least 20 percent (%) increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 millimeter (mm); progression of existing non-target lesions; or presence of new lesions. Median PFS was estimated using Kaplan-Meier method.
Time Frame Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 690
Median (95% Confidence Interval)
Unit of Measure: Days
254
(230 to 279)
2.Primary Outcome
Title PFS by Therapeutic Regimens
Hide Description PFS was assessed using RECIST v1.1 and is defined as the time from the first dose of indicated treatment to PD or death, whichever occurred first. Participants who did not progress or died while being followed were censored on the date of the last visit. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm; progression of existing non-target lesions; or presence of new lesions. Median PFS was estimated using Kaplan-Meier method.
Time Frame Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Here, number (n)= number of participants evaluable for the specified therapeutic regimen.
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 690
Median (95% Confidence Interval)
Unit of Measure: Days
Capecitabine monotherapy (n=246)
194
(176 to 224)
Capecitabine + bevacizumab (n=25)
391 [1] 
(129 to NA)
Capecitabine + irinotecan (n=106)
242
(177 to 276)
Capecitabine + irinotecan + bevacizumab (n= 91)
392
(316 to 525)
Capecitabine + oxaliplatin (n=173)
240
(206 to 291)
Capecitabine + oxaliplatin + bevacizumab (n= 49)
392
(210 to 442)
[1]
Only 1-sided confidence interval was planned to be calculated for this regimen.
3.Secondary Outcome
Title Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1
Hide Description Overall response is defined as a complete response (CR) or a partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. Participants were evaluated for tumor response per RECIST v1.1 and assessed by computed tomography (CT) or magnetic resonance imaging (MRI):CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than (<) 10 mm). No new lesions.PR was defined as greater than or equal to (>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time Frame Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 690
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
24.3
(21.2 to 27.7)
4.Secondary Outcome
Title Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1
Hide Description Clinical benefit was defined as having a confirmed CR, PR or stable disease (SD) for at least 24 weeks on study according to RECIST v1.1.CR: complete disappearance of all target lesions and non-target disease,with the exception of nodal disease.All nodes,both target and non-target, must decrease to normal (short axis <10 mm).No new lesions.PR: >=30% decrease under baseline of the sum of diameters of all target lesions.The short axis was used in the sum for target nodes,while the longest diameter was used in the sum for all other target lesions.No unequivocal progression of non-target disease.No new lesions.SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest sum diameters while on study.PD:at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions,or presence of new lesions.
Time Frame Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 690
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
82.9
(79.9 to 85.6)
5.Secondary Outcome
Title Percentage of Participants Who Underwent Metastasectomy
Hide Description Metastasectomy is the surgical removal of metastases, which are secondary cancerous growths that have spread from cancer originating in another organ in the body.
Time Frame Baseline up to 1254 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 663
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
6.2
(4.4 to 8.0)
6.Secondary Outcome
Title Mean Duration of Capecitabine Therapy
Hide Description [Not Specified]
Time Frame Baseline up to 1254 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 660
Mean (Standard Deviation)
Unit of Measure: Days
188.8  (171.71)
7.Secondary Outcome
Title Percentage of Participants With Dose Modification of Capecitabine
Hide Description [Not Specified]
Time Frame Baseline up to 1254 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title mCRC Participants
Hide Arm/Group Description:
Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
Overall Number of Participants Analyzed 690
Measure Type: Number
Unit of Measure: Percentage of participants
85.6
Time Frame Baseline up to Day 1254
Adverse Event Reporting Description Safety Population included all enrolled participants.
 
Arm/Group Title mCRC Participants
Hide Arm/Group Description Newly diagnosed mCRC participants, who received first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, were observed. The choice of therapy was based on exclusively the medical decision of the treating physician before study enrollment. The study protocol did not enforce treatment initiation and also did not specify any treatment regimen.
All-Cause Mortality
mCRC Participants
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
mCRC Participants
Affected / at Risk (%)
Total   55/882 (6.24%) 
Blood and lymphatic system disorders   
Anemia * 1  1/882 (0.11%) 
Febrile neutropenia * 1  1/882 (0.11%) 
Neutropenia * 1  3/882 (0.34%) 
Cardiac disorders   
Atrial fibrillation * 1  2/882 (0.23%) 
Heart failure * 1  3/882 (0.34%) 
Cardiopulmonary failure * 1  1/882 (0.11%) 
Myocardial ischaemia * 1  1/882 (0.11%) 
Gastrointestinal disorders   
Melaena * 1  1/882 (0.11%) 
Abdominal pain * 1  1/882 (0.11%) 
Bowel movement irregularity * 1  1/882 (0.11%) 
Diarrhoea * 1  3/882 (0.34%) 
Gastrointestinal haemorrhage * 1  1/882 (0.11%) 
Ileus * 1  2/882 (0.23%) 
Large intestine perforatio * 1  1/882 (0.11%) 
Subileus * 1  1/882 (0.11%) 
Thrombosis mesenteric vessel * 1  1/882 (0.11%) 
Vomiting * 1  1/882 (0.11%) 
General disorders   
Pyrexia * 1  1/882 (0.11%) 
Death * 1  1/882 (0.11%) 
General physical health deterioration * 1  1/882 (0.11%) 
Mucosal inflammation * 1  1/882 (0.11%) 
Hepatobiliary disorders   
Jaundice * 1  2/882 (0.23%) 
Immune system disorders   
Anaphylactic reaction * 1  1/882 (0.11%) 
Investigations   
White blood cell count decreased * 1  1/882 (0.11%) 
Metabolism and nutrition disorders   
Cachexia * 1  1/882 (0.11%) 
Dehydration * 1  2/882 (0.23%) 
Nervous system disorders   
Aphasia * 1  1/882 (0.11%) 
Cerebral ischaemia * 1  1/882 (0.11%) 
Cerebrovascular accident * 1  1/882 (0.11%) 
Peripheral neuropathy * 1  1/882 (0.11%) 
Paraparesis * 1  1/882 (0.11%) 
Renal and urinary disorders   
Acute kidney injury * 1  1/882 (0.11%) 
Renal failure * 1  1/882 (0.11%) 
Respiratory, thoracic and mediastinal disorders   
Pneumothorax * 1  1/882 (0.11%) 
Pulmonary embolism * 1  4/882 (0.45%) 
Skin and subcutaneous tissue disorders   
Cutaneous symptom * 1  1/882 (0.11%) 
Palmar-plantar erythrodysaesthesia syndroma * 1  2/882 (0.23%) 
Surgical and medical procedures   
Nephrostomy * 1  1/882 (0.11%) 
Vascular disorders   
Deep vein thrombosis * 1  1/882 (0.11%) 
Embolism * 1  1/882 (0.11%) 
thrombosis * 1  1/882 (0.11%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
mCRC Participants
Affected / at Risk (%)
Total   140/882 (15.87%) 
Gastrointestinal disorders   
Diarrhea * 1  98/882 (11.11%) 
Skin and subcutaneous tissue disorders   
Palmar-plantar erythrodysesthesia syndrome * 1  51/882 (5.78%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01696695     History of Changes
Other Study ID Numbers: ML27791
First Submitted: September 27, 2012
First Posted: October 1, 2012
Results First Submitted: September 22, 2016
Results First Posted: November 9, 2016
Last Update Posted: March 23, 2017