Trial Outcomes & Findings for An Observational Study of First-Line Capecitabine Based Chemotherapy in Participants With Metastatic Colorectal Cancer (NCT NCT01696695)

Last Updated: 2017-03-23

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

882 participants

Primary outcome timeframe

Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254

Results posted on

2017-03-23

Participant Flow

Participant milestones

Participant milestones
Measure	Metastatic Colorectal Carcinoma (mCRC) Participants 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.
Overall Study STARTED	882
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	882

Reasons for withdrawal

Reasons for withdrawal
Measure	Metastatic Colorectal Carcinoma (mCRC) Participants 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.
Overall Study Disease progression	373
Overall Study Death	29
Overall Study Adverse Event	74
Overall Study Withdrawal by Subject	92
Overall Study Lost to Follow-up	48
Overall Study Other	74
Overall Study Major Protocol Violation	192

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	mCRC Participants n=690 Participants 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.
Age, Continuous	64.9 years STANDARD_DEVIATION 10.51 • n=5 Participants
Sex: Female, Male Female	289 Participants n=5 Participants
Sex: Female, Male Male	401 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254

Population: ITT Population

Outcome measures

Outcome measures
Measure	mCRC Participants n=690 Participants 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.
Median Progression-free Survival (PFS)	254 Days Interval 230.0 to 279.0

PRIMARY outcome

Timeframe: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254

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

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.

Outcome measures

Outcome measures
Measure	mCRC Participants n=690 Participants 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.
PFS by Therapeutic Regimens Capecitabine monotherapy (n=246)	194 Days Interval 176.0 to 224.0
PFS by Therapeutic Regimens Capecitabine + bevacizumab (n=25)	391 Days Interval 129.0 to Only 1-sided confidence interval was planned to be calculated for this regimen.
PFS by Therapeutic Regimens Capecitabine + irinotecan (n=106)	242 Days Interval 177.0 to 276.0
PFS by Therapeutic Regimens Capecitabine + irinotecan + bevacizumab (n= 91)	392 Days Interval 316.0 to 525.0
PFS by Therapeutic Regimens Capecitabine + oxaliplatin (n=173)	240 Days Interval 206.0 to 291.0
PFS by Therapeutic Regimens Capecitabine + oxaliplatin + bevacizumab (n= 49)	392 Days Interval 210.0 to 442.0

SECONDARY outcome

Timeframe: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	mCRC Participants n=690 Participants 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.
Percentage of Participants With Overall Response as Assessed by Investigator Using RECIST v1.1	24.3 Percentage of participants Interval 21.2 to 27.7

SECONDARY outcome

Timeframe: Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254

Population: ITT Population.

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.

Outcome measures

Outcome measures
Measure	mCRC Participants n=690 Participants 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.
Percentage of Participants With Clinical Benefit as Assessed Using RECIST v1.1	82.9 Percentage of participants Interval 79.9 to 85.6

SECONDARY outcome

Timeframe: Baseline up to 1254 days

Population: ITT Population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.

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

Outcome measures

Outcome measures
Measure	mCRC Participants n=663 Participants 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.
Percentage of Participants Who Underwent Metastasectomy	6.2 Percentage of participants Interval 4.4 to 8.0

SECONDARY outcome

Timeframe: Baseline up to 1254 days

Population: ITT Population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.

Outcome measures

Outcome measures
Measure	mCRC Participants n=660 Participants 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.
Mean Duration of Capecitabine Therapy	188.8 Days Standard Deviation 171.71

SECONDARY outcome

Timeframe: Baseline up to 1254 days

Population: ITT Population.

Outcome measures

Outcome measures
Measure	mCRC Participants n=690 Participants 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.
Percentage of Participants With Dose Modification of Capecitabine	85.6 Percentage of participants

Adverse Events

mCRC Participants

Serious events: 55 serious events

Other events: 140 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	mCRC Participants n=882 participants at risk 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.
Blood and lymphatic system disorders Anemia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Blood and lymphatic system disorders Febrile neutropenia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Blood and lymphatic system disorders Neutropenia	0.34% 3/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Cardiac disorders Atrial fibrillation	0.23% 2/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Cardiac disorders Heart failure	0.34% 3/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Cardiac disorders Cardiopulmonary failure	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Cardiac disorders Myocardial ischaemia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Melaena	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Abdominal pain	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Bowel movement irregularity	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Diarrhoea	0.34% 3/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Ileus	0.23% 2/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Large intestine perforatio	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Subileus	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Thrombosis mesenteric vessel	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Gastrointestinal disorders Vomiting	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
General disorders Pyrexia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
General disorders Death	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
General disorders General physical health deterioration	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
General disorders Mucosal inflammation	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Hepatobiliary disorders Jaundice	0.23% 2/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Immune system disorders Anaphylactic reaction	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Investigations White blood cell count decreased	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Metabolism and nutrition disorders Cachexia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Metabolism and nutrition disorders Dehydration	0.23% 2/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Nervous system disorders Aphasia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Nervous system disorders Cerebral ischaemia	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Nervous system disorders Cerebrovascular accident	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Nervous system disorders Peripheral neuropathy	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Nervous system disorders Paraparesis	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Renal and urinary disorders Acute kidney injury	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Renal and urinary disorders Renal failure	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.45% 4/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Skin and subcutaneous tissue disorders Cutaneous symptom	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndroma	0.23% 2/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Surgical and medical procedures Nephrostomy	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Vascular disorders Deep vein thrombosis	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Vascular disorders Embolism	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Vascular disorders thrombosis	0.11% 1/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.

Other adverse events

Other adverse events
Measure	mCRC Participants n=882 participants at risk 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.
Gastrointestinal disorders Diarrhea	11.1% 98/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	5.8% 51/882 • Baseline up to Day 1254 Safety Population included all enrolled participants.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER