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

NCT ID: NCT01918852

Last Updated: 2018-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2018-03-31

Brief 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

Detailed 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.

Conditions

Colorectal Cancer; Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Capecitabine

Capecitabine 1250 mg/m2 for patients \< 70 years of age, and 1000 mg/m2 for patients ≥ 70 years of age, orally b.i.d. day 1-14 with or without bevacizumab 7.5 mg/kg i.v. day 1.

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

S1

S-1 30 mg/m2 orally b.i.d. irrespective of age, day 1-14 with or without bevacizumab 7.5 mg/kg i.v. day 1.

Group Type: EXPERIMENTAL

Teysuno

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Interventions

Capecitabine

Intervention Type: DRUG

Teysuno

Intervention Type: DRUG

Bevacizumab

Intervention Type: DRUG

Other Intervention Names

Xeloda; S1; Avastin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nordic Pharma SAS

INDUSTRY

Sponsor Role: collaborator

Dutch Colorectal Cancer Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cornelis JA Punt, Prof MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam Medical Centre

Locations

Medisch Centrum Alkmaar

Alkmaar, , Netherlands

Meander Medisch Centrum

Amersfoort, , Netherlands

Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Academic Medical Centre

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, , Netherlands

Countries

Netherlands

References

Kwakman JJM, van Werkhoven E, Simkens LHJ, van Rooijen JM, van de Wouw YAJ, Tije AJT, Creemers GM, Hendriks MP, Los M, van Alphen RJ, Polee MB, Muller EW, van der Velden AMT, van Voorthuizen T, Koopman M, Mol L, Punt CJA. Updated Survival Analysis of the Randomized Phase III Trial of S-1 Versus Capecitabine in the First-Line Treatment of Metastatic Colorectal Cancer by the Dutch Colorectal Cancer Group. Clin Colorectal Cancer. 2019 Jun;18(2):e229-e230. doi: 10.1016/j.clcc.2019.01.002. Epub 2019 Jan 29. No abstract available.

Reference Type: DERIVED

PMID: 30782413 (View on PubMed)

Kwakman JJM, Simkens LHJ, van Rooijen JM, van de Wouw AJ, Ten Tije AJ, Creemers GJM, Hendriks MP, Los M, van Alphen RJ, Polee MB, Muller EW, van der Velden AMT, van Voorthuizen T, Koopman M, Mol L, van Werkhoven E, Punt CJA. Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group. Ann Oncol. 2017 Jun 1;28(6):1288-1293. doi: 10.1093/annonc/mdx122.

Reference Type: DERIVED

PMID: 28383633 (View on PubMed)

Related Links

http://www.dccg.nl

Related Info

Other Identifiers

SALTO

Identifier Type: -

Identifier Source: org_study_id