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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01696695
• Collaborator: (none)
• Enrollment: 882
• Locations: 22
• Duration (Months): 41
• Patients Per Site: 40.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This observational study will evaluate the efficacy and safety of different capecitabine based chemotherapies, alone or in combination with other therapies, as first line treatment of metastatic colorectal cancer in participants during everyday clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Capecitabine; Drug: Chemotherapy

Study Design

• Study Type: Observational
• Actual Enrollment: 882 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Program for Assessment of Capecitabine (Xeloda) Based First-line Therapies in Metastatic Colorectal Cancer (AXEL Study)
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Metastatic Colorectal Carcinoma (mCRC) Participants Newly diagnosed mCRC participants, who will receive first line capecitabine based chemotherapy according to effective official Summary of Product Characteristics, will be observed. The choice of therapy is based exclusively on the medical decision of the treating physician before study enrollment. The study protocol does not enforce treatment initiation and also do not specify any treatment regimen.

Drug: Capecitabine; First line capecitabine based oral tablet treatment in line with the effective Summary of Product Characteristics; Other Names: Xeloda ; Drug: Chemotherapy; First line chemotherapy according to effective official Summary of Product Characteristics. The study protocol does not specify any particular therapy.

Outcome Measures

Primary Outcome Measures

1. Median Progression-free Survival (PFS) [Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254]

   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.

2. PFS by Therapeutic Regimens [Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1 [Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254]

   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.

2. Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1 [Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254]

   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.

3. Percentage of Participants Who Underwent Metastasectomy [Baseline up to 1254 days]

   Metastasectomy is the surgical removal of metastases, which are secondary cancerous growths that have spread from cancer originating in another organ in the body.

4. Mean Duration of Capecitabine Therapy [Baseline up to 1254 days]

5. Percentage of Participants With Dose Modification of Capecitabine [Baseline up to 1254 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with newly diagnosed mCRC who have started first-line capecitabine-based chemotherapy in accordance with the current Hungarian label

Exclusion Criteria:

• History of serious or unexpected reaction to fluoropyrimidine therapy

• Hypersensitivity to the active ingredient of Xeloda or to any of the excipients of the product, or to fluorouracil

• Known dihydropyrimidine dehydrogenase deficiency

• Pregnancy or lactation

• Inadequate bone marrow, hepatic or renal function

• Treatment with sorivudine or its chemical analogues (for example, brivudine)

• If any contraindication for any drug used in the combination treatment schedules is present, the drug in question cannot be used

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Szent Margit Hospital	Budapest		Hungary	1032
2	Fov.Onk.Peterfy S.Utcai Korh.-Rend.Int es Baleseti Kozp.	Budapest		Hungary	1076
3	Semmelweis Egyetem, II. Belgyógyászati Klinika	Budapest		Hungary	1088
4	Semmelweis Egyetem Aok; Iii.Sz. Belgyogyaszati Klinika	Budapest		Hungary	1125
5	Fövárosi Önkormányzat uzsoki utcai Kórház	Budapest		Hungary	1145
6	Kenezy Korhaz Rendelointezet	Debrecen		Hungary	4031
7	Petz Aladar Megyei Oktato Korhaz	Gyor		Hungary	9024
8	Békés Megyei Pándy Kálmán Kórház; Onkologiai tanszek	Gyula		Hungary	5700
9	Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont	Kecskemet		Hungary	6000
10	Pest Megyei Flor Korhaz; Oncology	Kistarcsa		Hungary	2143
11	Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly	Miskolc		Hungary	3501
12	Josa Andras Korhaz; Dept of Oncoradiology	Nyíregyháza		Hungary	4400
13	Pécsi Tudományegyetem Áok; Onkoterapias Intezet	Pecs		Hungary	7623
14	Szent Lázár Kórház	Salgótarján		Hungary	3100
15	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged		Hungary	6720
16	Szent Gyorgy Korhaz;Fejer Megyei	Szekesfehervar		Hungary	8000
17	Tolna Megyei Onkormanyzat Balassa Janos Korhaz	Szekszard		Hungary	7100
18	Dr. Bugyi Istvan Korhaz	Szentes		Hungary	6600
19	Vas Megyei Markusovszky Korhaz X; Oncoradiology	Szombathely		Hungary	9700
20	Szent Borbala Korhaz	Tatabanuya		Hungary	2800
21	Veszprem Megyei Csolnoky; Ferenc Korhaz	Veszprem		Hungary	8200
22	Zala megyei Önkormányzat Kórház és Rendelõintézet	Zalaegerszeg		Hungary	8900

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01696695
• Other Study ID Numbers: ML27791
• First Posted: Oct 1, 2012
• Last Update Posted: Mar 23, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Colorectal Neoplasms; Capecitabine

Study Results

Participant Flow

Arm/Group Title	Metastatic Colorectal Carcinoma (mCRC) Participants
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

Baseline Characteristics

Arm/Group Title	mCRC Participants
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 Participants	690
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (10.51)
Sex: Female, Male (Count of Participants)
Female	289 41.9%
Male	401 58.1%

Outcome Measures

1. Primary Outcome

Title	Median Progression-free Survival (PFS)
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

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	mCRC Participants
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.
Measure Participants	690
Median (95% Confidence Interval) [Days]	254

2. Primary Outcome

Title	PFS by Therapeutic Regimens
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

Outcome Measure Data

Analysis Population Description

ITT Population. Here, number (n)= number of participants evaluable for the specified therapeutic regimen.

Arm/Group Title	mCRC Participants
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.
Measure Participants	690
Capecitabine monotherapy (n=246)	194
Capecitabine + bevacizumab (n=25)	391
Capecitabine + irinotecan (n=106)	242
Capecitabine + irinotecan + bevacizumab (n= 91)	392
Capecitabine + oxaliplatin (n=173)	240
Capecitabine + oxaliplatin + bevacizumab (n= 49)	392

3. Secondary Outcome

Title	Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1
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

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	mCRC Participants
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.
Measure Participants	690
Number (95% Confidence Interval) [Percentage of participants]	24.3 3.5%

4. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1
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

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	mCRC Participants
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.
Measure Participants	690
Number (95% Confidence Interval) [Percentage of participants]	82.9 12%

5. Secondary Outcome

Title	Percentage of Participants Who Underwent Metastasectomy
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

Outcome Measure Data

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
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.
Measure Participants	663
Number (95% Confidence Interval) [Percentage of participants]	6.2 0.9%

6. Secondary Outcome

Title	Mean Duration of Capecitabine Therapy
Time Frame	Baseline up to 1254 days

Outcome Measure Data

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
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.
Measure Participants	660
Mean (Standard Deviation) [Days]	188.8 (171.71)

7. Secondary Outcome

Title	Percentage of Participants With Dose Modification of Capecitabine
Time Frame	Baseline up to 1254 days

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	mCRC Participants
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.
Measure Participants	690
Number [Percentage of participants]	85.6 12.4%

Adverse Events

Time Frame	Baseline up to Day 1254
Adverse Event Reporting Description	Safety Population included all enrolled participants.
Arm/Group Title	mCRC Participants
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	mCRC Participants
	Affected / at Risk (%)	# Events
Total	55/882 (6.2%)
Blood and lymphatic system disorders
Anemia	1/882 (0.1%)
Febrile neutropenia	1/882 (0.1%)
Neutropenia	3/882 (0.3%)
Cardiac disorders
Atrial fibrillation	2/882 (0.2%)
Heart failure	3/882 (0.3%)
Cardiopulmonary failure	1/882 (0.1%)
Myocardial ischaemia	1/882 (0.1%)
Gastrointestinal disorders
Melaena	1/882 (0.1%)
Abdominal pain	1/882 (0.1%)
Bowel movement irregularity	1/882 (0.1%)
Diarrhoea	3/882 (0.3%)
Gastrointestinal haemorrhage	1/882 (0.1%)
Ileus	2/882 (0.2%)
Large intestine perforatio	1/882 (0.1%)
Subileus	1/882 (0.1%)
Thrombosis mesenteric vessel	1/882 (0.1%)
Vomiting	1/882 (0.1%)
General disorders
Pyrexia	1/882 (0.1%)
Death	1/882 (0.1%)
General physical health deterioration	1/882 (0.1%)
Mucosal inflammation	1/882 (0.1%)
Hepatobiliary disorders
Jaundice	2/882 (0.2%)
Immune system disorders
Anaphylactic reaction	1/882 (0.1%)
Investigations
White blood cell count decreased	1/882 (0.1%)
Metabolism and nutrition disorders
Cachexia	1/882 (0.1%)
Dehydration	2/882 (0.2%)
Nervous system disorders
Aphasia	1/882 (0.1%)
Cerebral ischaemia	1/882 (0.1%)
Cerebrovascular accident	1/882 (0.1%)
Peripheral neuropathy	1/882 (0.1%)
Paraparesis	1/882 (0.1%)
Renal and urinary disorders
Acute kidney injury	1/882 (0.1%)
Renal failure	1/882 (0.1%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/882 (0.1%)
Pulmonary embolism	4/882 (0.5%)
Skin and subcutaneous tissue disorders
Cutaneous symptom	1/882 (0.1%)
Palmar-plantar erythrodysaesthesia syndroma	2/882 (0.2%)
Surgical and medical procedures
Nephrostomy	1/882 (0.1%)
Vascular disorders
Deep vein thrombosis	1/882 (0.1%)
Embolism	1/882 (0.1%)
thrombosis	1/882 (0.1%)
Other (Not Including Serious) Adverse Events
	mCRC Participants
	Affected / at Risk (%)	# Events
Total	140/882 (15.9%)
Gastrointestinal disorders
Diarrhea	98/882 (11.1%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	51/882 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.