S-1 Versus Capecitabine in the First Line Treatment of MCC Patients.

Colorectal Cancer Clinical Trial

— SALTO  

Official title:

S1 Versus Capecitabine in the First Line Treatment of Metastatic Colorectal Cancer Patients, the SALTO Randomised Phase III Study of the Dutch Colorectal Cancer Group. A Safety Evaluation of Oral Fluoropyrimidines

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01918852
• Other study ID #: SALTO
• Status: Completed
• Phase: Phase 3
• First received: June 24, 2013
• Last updated: March 13, 2018
• Start date: December 2013
• Est. completion date: March 2018

Study information

• Verified date: March 2018
• Source: Dutch Colorectal Cancer Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a two-arm randomised phase III trial. Patients will be randomised 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

Description:

Capecitabine, an oral fluoropyrimidine, has shown a comparable efficacy but a better tolerability compared to bolus 5-FU/LV. However, capecitabine has a higher incidence of hand-foot syndrome (HFS). HFS is characterized by erythema, dysesthesia and/or paresthesia of the palms of the hands or soles of feet. In advanced stage, desquamation, ulceration and blistering can occur. Although HFS is not life threatening, it can cause significant discomfort and impairment of function, especially in elderly patients. This adverse event is becoming particularly relevant since many patients may require the administration of capecitabine over prolonged periods of time.

S-1 (Teysuno®) is an oral fluoropyrimidine that has shown comparable efficacy to 5FU and capecitabine in gastrointestinal cancers but is associated with a much lower incidence of HFS. Studies on S-1 have mainly been performed in Asian patients,which population has known differences in tumour biology and toxicity compared to Western population. S-1 has shown comparable efficacy to other fluoropyrimidines as monotherapy or in combination chemotherapy schedules in several gastrointestinal tumors. However, given the lack of data from prospective studies on S-1 as monochemotherapy in metastatic colorectal cancer in Western patients, this study is designed to compare S-1 and capecitabine monotherapy in terms of safety, with particular interest in HFS, in metastatic colorectal cancer patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: March 2018
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 treatment with fluoropyrimidine monotherapy with or without bevacizumab.

• WHO performance status 0-2 (Karnofsky PS =70%)

• 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 previous systemic treatment for metastatic 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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastases

Intervention

Drug:
• Capecitabine

• Teysuno

• Bevacizumab

Locations

Country	Name	City	State
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Academic Medical Centre	Amsterdam
Netherlands	Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	OLVG	Amsterdam
Netherlands	VUMC	Amsterdam
Netherlands	Wilhelmina Ziekenhuis	Assen
Netherlands	Ziekenhuis Lievensberg	Bergen op Zoom
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Slingeland Ziekenhuis	Doetinchem
Netherlands	Catherina Ziekenhuis	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	St Jansdal	Harderwijk
Netherlands	Spaarne Ziekenhuis	Hoofddorp
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Antonius Ziekenhuis	Nieuwegein
Netherlands	Waterland Ziekenhuis	Purmerend
Netherlands	Sint Franciscus Gasthuis	Rotterdam
Netherlands	Vlietland Ziekenhuis	Schiedam
Netherlands	Orbis Medisch Centrum	Sittard
Netherlands	Tweesteden Ziekenhuis	Tilburg
Netherlands	University Medical Centre Utrecht	Utrecht
Netherlands	VieCuri Medisch Centrum	Venlo
Netherlands	Zaans Medisch Centrum	Zaandam

Sponsors (2)

Lead Sponsor	Collaborator
Dutch Colorectal Cancer Group	Nordic Pharma SAS

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of HFS in first line treatment	To determine the incidence of HFS in first line treatment with S-1 compared to capecitabine in patients with metastatic colorectal cancer.	HFS will be assessed every 3 weeks up to 6 months average.
Secondary	Grade 3 HFS	Incidence of grade 3 hand-foot syndrome, according to CTC 4.0.	HFS will be assessed every 3 weeks, up to 6 months average
Secondary	Progression-free survival	Time from randomisation until progression or death whichever comes first	Every 9 weeks, for 6 months (average)
Secondary	Overall toxicity	Adverse events graded accoording to the NCI CTCAE version 4	Every 3 weeks, for 6 months (average)
Secondary	Overall survival	From date of randomisation to death or last known to be alive	2 years
Secondary	Response rate	Response acccording to RECIST 1.1	Response will be assessed every 9 weeks, up to 6 months average.

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