Clinical trial • Phase III • Oncology
Trifluridine; Tipiracil hydrochloride for Metastatic colorectal cancer
Phase III trial of Trifluridine; Tipiracil hydrochloride for Metastatic colorectal cancer.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Metastatic colorectal cancer
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody|Small molecule
Key dates
- Initial CTIS Submission Date
- 18-09-2024
- First CTIS Authorization Date
- 15-10-2024
Trial design
Randomised, open-label, arm experimental: s 95005 (35 mg/m2/dose) administered orally bid, within 1 hour after completion of morning and evening meals, 5 days on/2 days off for 2 weeks followed by a 14-day rest (cycle repeated every 4 weeks) plus bevacizumab 5 mg/kg iv every 2 weeks (day 1 and day 15). arm active comparator: capecitabine 1250 mg/m² orally bid on days 1–14 of each cycle (starting dose may be reduced to 1000 mg/m²/dose per local practice), with bevacizumab 7.5 mg/kg iv on day 1 of each cycle (cycle repeated every 3 weeks).-controlled Phase III trial across 4 sites in Sweden, Slovakia, Denmark and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Arm experimental: S 95005 (35 mg/m2/dose) administered orally BID, within 1 hour after completion of morning and evening meals, 5 days on/2 days off for 2 weeks followed by a 14-day rest (cycle repeated every 4 weeks) plus bevacizumab 5 mg/kg IV every 2 weeks (Day 1 and Day 15). Arm active comparator: Capecitabine 1250 mg/m² orally BID on Days 1–14 of each cycle (starting dose may be reduced to 1000 mg/m²/dose per local practice), with bevacizumab 7.5 mg/kg IV on Day 1 of each cycle (cycle repeated every 3 weeks).
- Target Sample Size
- 382
Stratification factors
- ECOG performance status (0 vs. 1 vs. 2)
- Primary tumour localisation (right vs. left)
- Reason why the patient is not candidate to intensive therapy (clinical condition reason vs. non-clinical condition reason)
Eligibility
Recruits 382 Vulnerable population selected. Informed consent handled via subject information and informed consent forms; country-specific ICF documents are available (documents listed for Denmark, Sweden, Slovakia and Poland). No specific assent procedures for minors are specified in the available documents..
- Pregnancy Exclusion
- Pregnancy, breastfeeding or possibility of becoming pregnant during the study.
- Vulnerable Population
- Vulnerable population selected. Informed consent handled via subject information and informed consent forms; country-specific ICF documents are available (documents listed for Denmark, Sweden, Slovakia and Poland). No specific assent procedures for minors are specified in the available documents.
Inclusion criteria
- {"criterion_text":"- Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known.\n- RAS status based on local biological assessment of tumour biopsy must be available. If RAS status is not available at the time of randomisation, tumour biopsy must be available for RAS status determination (based on local biological assessment).\n- Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin\n- Patient is not a candidate for curative resection of metastatic lesions\n- No previous systemic anticancer therapy for unresectable metastatic colorectal cancer\n- ECOG (Eastern Cooperative Oncology Group) performance status ≤2.\n- Adequate organ function (renal, haematological, hepatic, coagulation) as described in the study protocol'"}
Exclusion criteria
- {"criterion_text":"- Pregnancy, breastfeeding or possibility of becoming pregnant during the study.\n- Participation in another interventional study within 4 weeks prior to the randomisation .\n- Patients who have not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to the randomisation.\n- Symptomatic central nervous system metastases.\n- Major surgery within 4 weeks prior to the randomisation.\n- Exclusion criteria related to S 95005 administration: History of allergic reactions attributed to compounds of similar composition to S 95005 or any of its excipients.\n- Any contraindication present in the SmPC of trifluridine/tipiracil\n- Exclusion criteria related to bevacizumab administration: Any contraindication present in the SmPC of bevacizumab\n- Exclusion criteria related to capecitabine administration: Any contraindication present in the SmPC of capecitabine"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Progression-free survival (PFS) based on investigator judgement","definition_or_measurement_approach":"Based on investigator judgement"}
Secondary endpoints
- {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Overall response rate (ORR)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Disease control rate (DCR)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Time to treatment failure (TTF)","definition_or_measurement_approach":""}
- {"endpoint_text":"- Safety and tolerability assessed by incidence of adverse events (AE), laboratory tests, physical examination and performance status (ECOG), vital signs, 12-leads ECG parameters","definition_or_measurement_approach":"Assessed by incidence of adverse events (AE), laboratory tests, physical examination, ECOG performance status, vital signs and 12-lead ECG parameters"}
- {"endpoint_text":"- Quality of life (QoL)","definition_or_measurement_approach":"Measured as quality-of-life outcomes (patient questionnaires). Patient-facing documents include QoL questionnaires (EORTC and EQ-5D-5L) listed in protocol documents"}
Recruitment
- Planned Sample Size
- 382
- Recruitment Window Months
- 75
- Consent Approach
- Informed consent obtained using subject information and informed consent forms; country-specific ICFs are provided (documents listed for Denmark, Sweden, Slovakia and Poland). Consent provided by the participant (adult); no age-specific assent procedures for minors are specified in the available documents.
Geography
- Total Number Of Sites
- 4
- Total Number Of Participants
- 84
Sweden
- Earliest CTIS Part Ii Submission Date
- 09-09-2024
- Latest Decision Or Authorization Date
- 16-10-2024
- Processing Time Days
- 37
- Number Of Sites
- 1
- Number Of Participants
- 10
Sites
- Site Name
- Region Joenkoepings Laen
- Department Name
- Oncology department
- Contact Person Name
- Karin Adolfsson
- Contact Person Email
- karin.adolfsson@rjl.se
Slovakia
- Earliest CTIS Part Ii Submission Date
- 09-09-2024
- Latest Decision Or Authorization Date
- 15-10-2024
- Processing Time Days
- 36
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Vychodoslovensky Onkologicky Ustav a.s.
- Department Name
- Oddelenie klinickej onkologie
- Contact Person Name
- Igor ANDRASINA
- Contact Person Email
- grega@vou.sk
Denmark
- Earliest CTIS Part Ii Submission Date
- 10-10-2024
- Latest Decision Or Authorization Date
- 15-10-2024
- Processing Time Days
- 5
- Number Of Sites
- 1
- Number Of Participants
- 36
Sites
- Site Name
- Region Midtjylland
- Department Name
- Oncology department
- Contact Person Name
- Lone Duval
- Contact Person Email
- londuv@rm.dk
Poland
- Earliest CTIS Part Ii Submission Date
- 09-09-2024
- Latest Decision Or Authorization Date
- 08-11-2024
- Processing Time Days
- 60
- Number Of Sites
- 1
- Number Of Participants
- 34
Sites
- Site Name
- Specjalistyczny Szpital Onkologiczny Nu-Med Sp. z o.o.
- Department Name
- Pododdzial Chemioterapii
- Contact Person Name
- Magdalena Ciążyńska
- Contact Person Email
- ciazynska.magdalena@gmail.com
Sponsor
Primary sponsor
- Full Name
- Institut De Recherches Internationales Servier IRIS
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- France
Contract research organisations
- Name
- IQVIA Limited
- Responsibilities
- Clinical monitoring for DNK, POL, SWE
- Name
- Clario
- Responsibilities
- e-PRO
- Name
- Cerba Research
- Responsibilities
- Central laboratory
- Name
- Median Technologies
- Responsibilities
- Medical image analysis/ review - X-ray, MRI, ultrasound, etc.
- Name
- Theradis Pharma
- Responsibilities
- IRS (Randomisation & Drug Kit management)
- Name
- SAGA Diagnostics AB
- Responsibilities
- Third part lab for BRAF analysis
- Name
- Heva
- Responsibilities
- 6
Third parties
- {"country":"Switzerland","full_name":"Clario","duties_or_roles":"e-PRO","organisation_type":"Health care"}
- {"country":"France","full_name":"Median Technologies","duties_or_roles":"Medical image analysis/ review - X-ray, MRI, ultrasound, etc.","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"Central laboratory","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Clinical monitoring for DNK, POL, SWE","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Heva","duties_or_roles":"6","organisation_type":"Pharmaceutical company"}
- {"country":"Sweden","full_name":"SAGA Diagnostics AB","duties_or_roles":"Third part lab for BRAF analysis","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Theradis Pharma","duties_or_roles":"IRS (Randomisation & Drug Kit management)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Lonsurf 20 mg/8.19 mg film-coated tablets
- Active Substance
- Trifluridine; Tipiracil hydrochloride
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (marketing authorisation present)
- Starting Dose
- 35 mg/m2/dose orally BID (as S 95005 in experimental arm)
- Dose Levels
- 35 mg/m2/dose BID (max 70 mg/m2/day)
- Frequency
- BID (5 days on/2 days off schedule in 2 weeks, then 14 days rest; cycle repeated every 4 weeks)
- Maximum Dose
- 70 mg/m2/day
- Investigational Product Name
- Lonsurf 15 mg/6.14 mg film-coated tablets
- Active Substance
- Trifluridine; Tipiracil hydrochloride
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (marketing authorisation present)
- Starting Dose
- 35 mg/m2/dose orally BID (as S 95005 in experimental arm)
- Dose Levels
- 35 mg/m2/dose BID (max 70 mg/m2/day)
- Frequency
- BID (5 days on/2 days off schedule in 2 weeks, then 14 days rest; cycle repeated every 4 weeks)
- Maximum Dose
- 70 mg/m2/day
- Investigational Product Name
- Avastin 25 mg/ml concentrate for solution for infusion.
- Active Substance
- Bevacizumab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Authorised (marketing authorisation present)
- Starting Dose
- 5 mg/kg IV every 2 weeks in combination with S95005 (or 7.5 mg/kg IV every 3 weeks in combination with capecitabine arm)
- Dose Levels
- 5 mg/kg q2w (with S95005) or 7.5 mg/kg q3w (with capecitabine)
- Frequency
- Every 2 weeks (5 mg/kg) or every 3 weeks (7.5 mg/kg) depending on arm
- Maximum Dose
- 7.5 mg/kg
- Investigational Product Name
- Xeloda 150 mg film-coated tablets
- Active Substance
- Capecitabine
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (marketing authorisation present)
- Starting Dose
- 1250 mg/m² orally BID on Days 1–14 of each cycle (may be started at 1000 mg/m²/dose per local practice)
- Dose Levels
- 1250 mg/m²/dose BID (Days 1–14); starting dose may be reduced to 1000 mg/m²/dose
- Frequency
- BID on Days 1–14 of each 3-week cycle
- Maximum Dose
- 2500 mg/m2/day
- Investigational Product Name
- Xeloda 500 mg film-coated tablets
- Active Substance
- Capecitabine
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (marketing authorisation present)
- Starting Dose
- 1250 mg/m² orally BID on Days 1–14 of each cycle (may be started at 1000 mg/m²/dose per local practice)
- Dose Levels
- 1250 mg/m²/dose BID (Days 1–14); starting dose may be reduced to 1000 mg/m²/dose
- Frequency
- BID on Days 1–14 of each 3-week cycle
- Maximum Dose
- 2500 mg/m2/day
- Combination Treatment
- Yes
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