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

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ClinicalTrials.gov Identifier: NCT01918852
Recruitment Status : Completed
First Posted : August 8, 2013
Last Update Posted : March 14, 2018
Sponsor:
Collaborator:
Nordic Pharma SAS
Information provided by (Responsible Party):
Dutch Colorectal Cancer Group

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

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastases Drug: Capecitabine Drug: Teysuno Drug: Bevacizumab Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 161 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : December 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.
Drug: Capecitabine
Other Name: Xeloda

Drug: Bevacizumab
Other Name: Avastin

Experimental: 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.
Drug: Teysuno
Other Name: S1

Drug: Bevacizumab
Other Name: Avastin




Primary Outcome Measures :
  1. Incidence of HFS in first line treatment [ Time Frame: HFS will be assessed every 3 weeks up to 6 months average. ]
    To determine the incidence of HFS in first line treatment with S-1 compared to capecitabine in patients with metastatic colorectal cancer.


Secondary Outcome Measures :
  1. Grade 3 HFS [ Time Frame: HFS will be assessed every 3 weeks, up to 6 months average ]
    Incidence of grade 3 hand-foot syndrome, according to CTC 4.0.

  2. Progression-free survival [ Time Frame: Every 9 weeks, for 6 months (average) ]
    Time from randomisation until progression or death whichever comes first

  3. Overall toxicity [ Time Frame: Every 3 weeks, for 6 months (average) ]
    Adverse events graded accoording to the NCI CTCAE version 4

  4. Overall survival [ Time Frame: 2 years ]
    From date of randomisation to death or last known to be alive

  5. Response rate [ Time Frame: Response will be assessed every 9 weeks, up to 6 months average. ]
    Response acccording to RECIST 1.1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01918852


Locations
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Netherlands
Medisch Centrum Alkmaar
Alkmaar, Netherlands
Meander Medisch Centrum
Amersfoort, Netherlands
Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, Netherlands, 1066 CX
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
Sponsors and Collaborators
Dutch Colorectal Cancer Group
Nordic Pharma SAS
Investigators
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Principal Investigator: Cornelis JA Punt, Prof MD PhD Amsterdam Medical Centre

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dutch Colorectal Cancer Group
ClinicalTrials.gov Identifier: NCT01918852     History of Changes
Other Study ID Numbers: SALTO
First Posted: August 8, 2013    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Dutch Colorectal Cancer Group:
Hand-foot syndrome
Toxicity
Fluoropyrimidine
Capecitabine
Teysuno
S1

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Capecitabine
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action