The primary objective is to determine the incidence of HFS in first line treatment with S-1 compared to capecitabine in patients with metastatic colorectal cancer. Secondary objectives include a comparison of efficacy.
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the incidence of HFS in first line treatment with S-1 compared to
capecitabine in patients with metastatic colorectal cancer.
Secondary outcome
To evaluate and assess:
* Incidence of grade 3 hand-foot syndrome
* Incidence of other toxicities
* Progression-free survival
* Response rate
* Overall survival
Background summary
Nowadays, standard 1st-line treatment for patients with metastatic colorectal
cancer currently consists of fluoropyrimidine-containing chemotherapy plus
bevacizumab.
It has been shown that first-line fluoropyrimidine monotherapy is a valid
alternative for combination chemotherapy in the majority of metastatic
colorectal cancer patients. Upfront combination chemotherapy is only indicated
in patients in whom tumour shrinkage is the primary goal or who are less likely
to be eligible for salvage treatments. Bevacizumab is considered as part of the
first-line standard treatment, and has also shown a benefit when added to
fluoropyrimidine monotherapy. However bevacizumab may not be indicated in all
patients.
Study objective
The primary objective is to determine the incidence of HFS in first line
treatment with S-1 compared to capecitabine in patients with metastatic
colorectal cancer. Secondary objectives include a comparison of efficacy.
Study design
The study is a two-arm randomised phase III trial. Eligible patients will be
randomised after informed consent has been obtained.
Patients will be randomised 1:1 to receive capecitabine (arm A) or S-1 (arm B).
Bevacizumab may be added according to the choice of the investigator. Patients
will be followed 3-weekly at the outpatient clinic, toxicity will be assessed
according to study protocol guidelines. Patients will be evaluated every 3
cycles for response. Upon disease progression patients will be treated
according to the local investigators choice.
Intervention
Teysuno 2dd versus Capecitabine 2dd with or without bevacizumab
Study burden and risks
A patient diary has to be completed each cycle.
Scheveningseweg 56 F
Den Haag 2517 KW
NL
Scheveningseweg 56 F
Den Haag 2517 KW
NL
Listed location countries
Age
Inclusion criteria
* Histological proof of colorectal cancer.;* Distant metastases (patients with only local recurrence are not eligible);* Unidimensionally measurable disease (*1 cm on spiral CT scan or *2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation.;* In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.;* Age * 18 years ;* Planned first line treatment with capecitabine monotherapy with or without bevacizumab. ;* WHO performance status 0-2 (Karnofsky PS *70%);;* Laboratory values obtained within 2 weeks prior to randomisation:;* adequate bone marrow function (Hb * 6.0 mmol/L, absolute neutrophil count *1.5 x 109/L, platelets * 100 x 109/L), renal function (serum creatinine * 1.5x ULN and creatinine clearance, Cockroft formula, *30 ml/min), liver function (serum bilirubin * 2 x ULN, serum transaminases * 3 x ULN without presence of liver metastases or * 5x ULN with presence of liver metastases).;* Life expectancy > 12 weeks.;* Negative pregnancy test in women with childbearing potential.;* Expected adequacy of follow-up.;* Institutional Review Board approval.;* Written informed consent.
Exclusion criteria
* Prior adjuvant treatment for stage II/III colorectal cancer completed within 6 months prior to randomisation.;* Any prior adjuvant treatment after resection of distant metastases.;* Any prior systemic treatment for advanced disease.;* History or clinical signs/symptoms of CNS metastases.;* History of a second malignancy <5 years with the exception of adequately treated carcinoma of cervix or basal/squamous cell carcinoma of skin.;* Previous intolerance of capecitabine.;* Known dihydropyrimidine dehydrogenase (DPD) deficiency or treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.;* Planned radical resection of metastases after downsizing by systemic treatment.;* Significant cardiovascular disease < 1 yr before randomisation (symptomatic congestive heart failure, myocardial ischemia or infarction, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, arterial thrombosis, cerebrovascular event, pulmonary embolism).;* Any significant cardiovascular events during previous fluoropyrimidine therapy.;* Chronic active infection.;* Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs.;* Any impairment of gastrointestinal function or *disease that may significantly impair the absorption of oral drugs (i.e. uncontrolled nausea, vomiting, diarrhoea (defined as ³CTC grade 2), malabsorption syndrome, bowel obstruction, or inability to swallow tablets).;* Concomitant treatments: concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation; concurrent treatment with any other anti-cancer therapy. ;* Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).;In case of treatment with bevacizumab:;* Uncontrolled hypertension, i.e. consistently > 150/100 mmHg.;* Use of * 3 antihypertensive drugs.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-002147-28-NL |
| CCMO | NL45030.018.13 |