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

NCT01918852 | Completed Phase 3 DMC

• 1 other identifier: SALTO
• Study Type: interventional
• Target: 161
• Locations: 1 country
• Sites: 24

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

Conditions

Colorectal Cancer; Metastases

Keywords

Hand-foot syndrome; Toxicity; Fluoropyrimidine; Capecitabine; Teysuno; S1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Grade 3 HFS

  HFS will be assessed every 3 weeks, up to 6 months average

• Progression-free survival

  Every 9 weeks, for 6 months (average)

• Overall toxicity

  Every 3 weeks, for 6 months (average)

• Overall survival

  2 years

• Response rate

  Response will be assessed every 9 weeks, up to 6 months average.

Study Arms (2)

Capecitabine

ACTIVE COMPARATOR

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.

Drug: Capecitabine; Drug: Bevacizumab

S1

EXPERIMENTAL

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.

Drug: Teysuno; Drug: Bevacizumab

Interventions

Capecitabine DRUG

Also known as: Xeloda

Capecitabine

Teysuno DRUG

Also known as: S1

S1

Bevacizumab DRUG

Also known as: Avastin

Capecitabine; S1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dutch Colorectal Cancer Group: lead
• Nordic Pharma SAS: collaborator

Study Sites (24)

Medisch Centrum Alkmaar

Alkmaar, Netherlands

Location

Meander Medisch Centrum

Amersfoort, Netherlands

Location

Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Academic Medical Centre

Amsterdam, Netherlands

Location

OLVG

Amsterdam, Netherlands

Location

VUMC

Amsterdam, Netherlands

Location

Wilhelmina Ziekenhuis

Assen, Netherlands

Location

Ziekenhuis Lievensberg

Bergen op Zoom, Netherlands

Location

Amphia Ziekenhuis

Breda, Netherlands

Location

Slingeland Ziekenhuis

Doetinchem, Netherlands

Location

Catherina Ziekenhuis

Eindhoven, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

St Jansdal

Harderwijk, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Waterland Ziekenhuis

Purmerend, Netherlands

Location

Sint Franciscus Gasthuis

Rotterdam, Netherlands

Location

Vlietland Ziekenhuis

Schiedam, Netherlands

Location

Orbis Medisch Centrum

Sittard, Netherlands

Location

Tweesteden Ziekenhuis

Tilburg, Netherlands

Location

University Medical Centre Utrecht

Utrecht, Netherlands

Location

VieCuri Medisch Centrum

Venlo, Netherlands

Location

Zaans Medisch Centrum

Zaandam, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 30782413 DERIVED

• 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.

  PMID: 28383633 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Hand-Foot Syndrome

Interventions

Capecitabine; tegafur-gimeracil-oteracil; S 1 (combination); Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cornelis JA Punt, Prof MD PhD

  Amsterdam Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2013
• First Posted: August 8, 2013
• Study Start: December 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2018
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

NL (24)