A Study Evaluating S 95005 Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Colorectal Cancer Who Are Non-eligible for Intensive Therapy

NCT ID: NCT02743221

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-29
• Study Completion Date: 2020-09-01

Brief Summary

The main purpose of this study is to evaluate the progression-free survival (PFS) in patients receiving S 95005 + bevacizumab (experimental arm) or capecitabine + bevacizumab (control arm) as first-line treatment for unresectable metastatic colorectal cancer in patients non-eligible for intensive therapy.

Conditions

Metastatic Colorectal Cancer

Study Design

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

Study Groups

Trifluridine/tipiracil + bevacizumab

Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride.

Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab.

Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks.

Group Type: EXPERIMENTAL

Trifluridine/tipiracil + bevacizumab

Intervention Type: DRUG

Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Capecitabine + bevacizumab

Capecitabine was administered at 1250 mg/m² orally BID (bis in die)on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks

Group Type: ACTIVE_COMPARATOR

Capecitabine + bevacizumab

Intervention Type: DRUG

Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Interventions

Trifluridine/tipiracil + bevacizumab

Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.

Intervention Type: DRUG

Capecitabine + bevacizumab

Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained.
• Has ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1 or 2 at the time of the randomisation.
• Has definitive histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
• RAS status must have been determined (mutant or wild).
• Has at least one measurable metastatic lesion.
• No previous systemic anticancer therapy for unresectable metastatic colorectal cancer.
• Previous adjuvant (or neoadjuvant for patients with rectal cancer) chemotherapy is allowed only if if it has been completed more than 6 months before start of study treatment.
• Patient is not a candidate for combination chemotherapy with irinotecan or oxaliplatin, or for curative resection of metastatic lesions.
• Is able to take medication orally (i.e., no feeding tube).
• Has adequate organ function.
• Coagulation parameters in normal limit (or in therapeutic limit for patients treated with anticoagulant drugs).
• Women of childbearing potential must have been tested negative in a serum pregnancy test. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use a highly effective method of birth control. Women and female partners using hormonal contraceptive must also use a barrier method.

Exclusion Criteria

• Is a pregnant or lactating female.
• Has certain serious illness or serious medical condition(s) as described in the protocol.
• Has had certain other recent treatment e.g. major surgery, field radiation, received investigational agent, within the specified time frames prior to randomisation.
• Has previously received Trifluridine/tipiracil or history of allergic reactions attributed to compounds of similar composition to Trifluridine/tipiracil or any of its excipients.
• Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• Has contra-indication to bevacizumab or capecitabine.

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

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric Van Custem, Prof

Role: PRINCIPAL_INVESTIGATOR

Leuven Cancer Institute, University Hospitals Leuven

Locations

Chris O'Brien Lifehouse Oncology

Camperdown, , Australia

Austin Hospital Olivia Newton-John Cancer & Wellness Centre

Heidelberg, , Australia

Western Health, Sunshine Hospital

Saint Albans, , Australia

The Queen Elizabeth Hospital Haematology and Oncology Unit

Woodville, , Australia

Grand Hôpital de Charleroi Oncologie-Hématologie

Charleroi, , Belgium

UZ Leuven Campus Gasthuisberg Digestieve Oncologie

Leuven, , Belgium

CHC Saint-Joseph Oncologie-Hématoimmunopathologie

Liège, , Belgium

Hospital do Câncer de Barretos - Fundação Pio XII

Barretos, , Brazil

Centro de Pesquisa Hospital de Caridade de Ijuí

Ijuí, , Brazil

Instituto Nacional do Câncer - INCA Unidade de Pesquisa ClínicaInstituto Nacional do Câncer - INCA Unidade de Pesquisa Clínica

Rio de Janeiro, , Brazil

Hospital de Base, Centro Intergrado de Pesquisa

São José do Rio Preto, , Brazil

Instituto do Câncer do Estado de São Paulo - ICESP, Núcleo de Pesquisa

São Paulo, , Brazil

Rigshospitalet - Dpt of Oncology

Copenhagen, , Denmark

Odense Universitetshospital - Department of Oncology

Odense, , Denmark

CHU Jean Minjoz, Service d'oncologie médicale

Besançon, , France

Hôpital Saint Antoine, oncology department

Paris, , France

Centre René Gauducheau, Oncologie Médicale

Saint-Herblain, , France

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Schwerpunktpraxis für Hämatologie und Onkologie

Magdeburg, , Germany

Städtisches Krankenhaus München Neuperlach, Klinik für Onkologie und Hämatologie

Munich, , Germany

Fondazione Poliambulanza Istituto Ospedaliero, Clinical Oncology

Brescia, , Italy

A.O.U. SanMartino-IST, Unità Operativa Oncologia Medica 1

Genova, , Italy

A.O. Ospedale Niguarda Ca' Granda-Milano, Department of Onco-Haematology- Onoclogia Falck

Milan, , Italy

Seconda Università degli Studi di Napoli, U.O.C. di Oncologia Medica ed Ematologia

Naples, , Italy

.O.U. Pisana-Ospedale Santa Chiara, U.O. di Oncologia Medica 2

Pisa, , Italy

AMC Academisch Medisch Centrum Medische Oncologie

Amsterdam, , Netherlands

Amphia Ziekenhuis, Interne Geneeskunde/Oncologie, Langendijk 75

Breda, , Netherlands

Catharina Ziekenhuis, Interne Geneeskunde/Oncologie

Eindhoven, , Netherlands

Martini Ziekenhuizen, Interne Geneeskunde/Oncologie, Van Swietenplein 1

Groningen, , Netherlands

Tergooi Hilversum, Medische Oncologie, Van Riebeeckweg 212

Hilversum, , Netherlands

Zuyderland Medisch Centrum Interne Geneeskunde

Sittard, , Netherlands

Sint Antonius Ziekenhuis Interne Geneeskunde/Oncologie

Utrecht, , Netherlands

VieCurie Medisch Centrum, Interne Geneeskunde, Tegelseweg 210

Venlo, , Netherlands

Isala Klinieken, Medische oncologie, Dokter Van Heeweg 2

Zwolle, , Netherlands

Szpitale Pomorskie Sp. z o.o. Oddzial Onkologii i Radioterapii

Gdynia, , Poland

SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii

Krakow, , Poland

Centralny Szpital Kliniczny MSW Klinika Onkologii i Hematologii

Warsaw, , Poland

NZOZ MAGODENT Oddzial Onkologii Klinicznej / Chemioterapii

Warsaw, , Poland

Russian Cancer Research Center n.a. NN Blokhin

Moscow, , Russia

Moscow City Oncology Hospital # 62, Chemotherapy

Moscow, , Russia

Russian Cancer Research Center n.a. NN Blokhin, Department of Research for New Antitumour Medicines

Moscow, , Russia

Scientific Centre for Specialized Medical Care (oncological)

Saint Petersburg, , Russia

Hospital Valle de Hebrón, Servicio de Oncología

Barcelona, , Spain

Hospital Universitario Reina Sofia, Deparatmento Oncología Médica

Córdoba, , Spain

Instituto Catalan De Oncología, Hospitalet de Llobregat

L'Hospitalet de Llobregat, , Spain

Hospital Universitario Gregorio Maranon

Madrid, , Spain

Hospital Ramón y Cajal, Oncología Médica

Madrid, , Spain

H. Universitario La Paz Oncología Médica

Madrid, , Spain

Hospital General Universitario, Oncología Médica

Málaga, , Spain

Complejo Hospitalario de Navarra, Oncología Médica

Pamplona, , Spain

The Beatson West of Scotland Cancer Centre GI cancers

Glasgow, , United Kingdom

Leicester Royal Infirmary, The HOPE Clinical Trials Unit

Leicester, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Imperial healthcare NHS Trust Charing Cross Hospital

London, , United Kingdom

Christie Hospital NHS Foundation Trust, GI & Endocrine

Manchester, , United Kingdom

Mount Vernon Hospital Department of Oncology

Northwood, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

Australia; Belgium; Brazil; Denmark; France; Germany; Italy; Netherlands; Poland; Russia; Spain; United Kingdom

References

Van Cutsem E, Danielewicz I, Saunders MP, Pfeiffer P, Argiles G, Borg C, Glynne-Jones R, Punt CJA, Van de Wouw AJ, Fedyanin M, Stroyakovskiy D, Kroening H, Garcia-Alfonso P, Wasan H, Falcone A, Fougeray R, Egorov A, Amellal N, Moiseyenko V. First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study. Br J Cancer. 2022 Jun;126(11):1548-1554. doi: 10.1038/s41416-022-01737-2. Epub 2022 Apr 19.

Reference Type: BACKGROUND

PMID: 35440667 (View on PubMed)

Van Cutsem E, Danielewicz I, Saunders MP, Pfeiffer P, Argiles G, Borg C, Glynne-Jones R, Punt CJA, Van de Wouw AJ, Fedyanin M, Stroyakovskiy D, Kroening H, Garcia-Alfonso P, Wasan H, Falcone A, Kanehisa A, Egorov A, Aubel P, Amellal N, Moiseenko V. Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study. Ann Oncol. 2020 Sep;31(9):1160-1168. doi: 10.1016/j.annonc.2020.05.024. Epub 2020 Jun 1.

Reference Type: DERIVED

PMID: 32497736 (View on PubMed)

Provided Documents

Document Type: Study Protocol

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Document Type: Statistical Analysis Plan

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Study Documents

Document Type: Individual Participant Data Set

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Document Type: Study Protocol

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Document Type: Statistical Analysis Plan

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Document Type: Informed Consent Form

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Document Type: Clinical Study Report

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Document Type: study-level clinical trial data

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Other Identifiers

2015-004544-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL2-95005-002

Identifier Type: -

Identifier Source: org_study_id