Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy.

Metastatic Colorectal Cancer Clinical Trial

— SOLSTICE  

Official title:

An Open-label, Randomised, Phase III Study cOmparing trifLuridine/Tipiracil (S 95005) in Combination With Bevacizumab to Capecitabine in Combination With Bevacizumab in firST-line Treatment of Patients With metastatIC Colorectal Cancer Who Are Not candidatE for Intensive Therapy (SOLSTICE Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03869892
• Other study ID #: CL3-95005-006
• Secondary ID: 2017-004059-22U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 21, 2019
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to demonstrate the superiority of S 95005 in combination with bevacizumab over capecitabine in combination with bevacizumab.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 856
• Est. completion date: June 30, 2024
• Est. primary completion date: June 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Has definitive histologically confirmed adenocarcinoma of the colon or rectum (all other histological types are excluded). Primary tumour localisation must be known.

2. 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).

3. Patient is not a candidate for standard full dose combination chemotherapy with irinotecan or oxaliplatin

4. Patient is not a candidate for curative resection of metastatic lesions.

5. No previous systemic anticancer therapy for unresectable metastatic colorectal cancer.

6. ECOG (Eastern Cooperative Oncology Group) performance status =2.

7. Adequate organ function (renal, haematological, hepatic, coagulation) as described in the study protocol'

Exclusion Criteria:

8. Pregnancy, breastfeeding or possibility of becoming pregnant during the study.

9. Participation in another interventional study within 4 weeks prior to the randomisation .

10. Patients who have not recovered from clinically relevant non-hematologic CTCAE grade = 3 toxicity of previous anticancer therapy prior to the randomisation.

11. Symptomatic central nervous system metastases.

12. Major surgery within 4 weeks prior to the randomisation.

Exclusion criteria related to S 95005 administration:

13. History of allergic reactions attributed to compounds of similar composition to S 95005 or any of its excipients.

14. Any contraindication present in the SmPC of trifluridine/tipiracil

Exclusion criteria related to bevacizumab administration:

15. Any contraindication present in the SmPC of bevacizumab

Exclusion criteria related to capecitabine administration:

16. Any contraindication present in the SmPC of capecitabine

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Trifluridine/tipiracil hydrochloride (S95005)
Film-coated tablets of S 95005 (35 mg/m²/dose) will be administered orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest; This treatment cycle will be repeated every 4 weeks.
• Capecitabine
Film-coated tablets, Capecitabine (1250 mg/m²/dose) will be administered orally BID on Days 1-14 of each cycle. This treatment cycle will be repeated every 3 weeks.

Biological:
• Bevacizumab experimental
Concentrate for solution for infusion, Bevacizumab (5 mg/kg, IV) administered every 2 weeks (Day 1 and Day 15). This treatment cycle will be repeated every 4 weeks.
• Bevacizumab control
Concentrate for solution for infusion, Bevacizumab (7.5 mg/kg, IV) will be administered on Day 1 of each cycle.This treatment cycle will be repeated every 3 weeks.

Locations

Country	Name	City	State
Argentina	Centro de Oncología e Investigación de Buenos Aires COIBA	Berazategui
Argentina	Fundación Favaloro Oncology Unit	Buenos Aires
Argentina	Hospital Universitario CEMIC Servicio de Oncología, Unidad de tumores gastrointestinales	Ciudad Autonoma de Buenos aires
Argentina	Instituto Alexander Fleming	Ciudad Autonoma de Buenos aires
Argentina	Hospital de Gastroenterología Dr. Carlos Borino Udaondo Oncology Unit	Ciudad Autónoma de Buenos Aires
Argentina	Centro Oncológico Riojano Integral CORI Fundación CORI para la Investigación y Prevención del Cáncer	La Rioja
Argentina	Fundación COIR Centro Oncológico de Interación Regional	Mendoza
Argentina	Instituto de Oncología de Rosario	Santa Fe
Argentina	ISIS Centro especializado	Santa Fe
Argentina	Centro Médico San Roque	Tucumán
Australia	Blacktown Hospital Cancer and Haematology Centre	Blacktown
Australia	Frankston Private Peninsula and Southeast Oncology Group	Frankston
Australia	Lake Macquarie Private Hospital	Gateshead
Australia	St George Hospital St George Hospital Cancer Care Centre	Kogarah
Australia	Adventist HealthCare Integrated Cancer Centre	Wahroonga
Australia	Southern Medical Day Care Centre	Wollongong
Austria	Med. Universität Graz Klinische Abteilung für Onkologie	Graz
Austria	Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V	Innsbruck
Austria	Ordensklinikum Linz Barmherzige Schwestern Interne I	Linz
Austria	Landeskrankenhaus (SALK) Universitätsklinik für Innere Medizin III (SALK)	Salzburg
Austria	Universitätsklinikum St. Pölten Klinische Abteilung für Innere Medizin I	St. Poelten
Austria	Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie	Wien
Brazil	Hospital do Câncer de Barretos - Fundação Pio XII Unidade de Pesquisa Clínica	Barretos
Brazil	Cenantron - Clinica	Belo Horizonte
Brazil	Sirio Libanes DF - Centro de Oncologia de Braslia do Sirio- Centro Intergrado de Pesquisa	Brasília
Brazil	Centro de Pesquisa Hospital de Caridade de Ijuí Unidade de Pesquisa Clínica	Ijuí
Brazil	Hospital Mae de Deus Oncologia	Porto Alegre
Brazil	Hospital São Rafael Centro Intergrado de Pesquisa	Salvador
Brazil	CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncol Centro Intergrado de Pesquisa	Santo André
Brazil	Hospital de Base Centro Integrado de Pesquisa	São José Do Rio Preto
Brazil	Hospital A C Camargo Unidade de Pesquisa Clinica	São Paulo
Brazil	ICESP - Instituto do Câncer do Estado de São Paulo Centro Integrado de Pesquisa	São Paulo
Bulgaria	"Complex oncology center - Burgas" EOOD Department of medical oncology	Burgas
Bulgaria	"Multiprofile hosp. for active treatmen Dr. Tota Venkova" AD Department of medical oncology	Gabrovo
Bulgaria	"Complex oncology center - Plovdiv" EOOD, IInd base Dpt. of Med. oncology and onc. diseases in gastroenterology	Plovdiv
Bulgaria	"Medical Center Nadezhda Clinical" EOOD Medical Oncology Department	Sofia
Bulgaria	"UMHAT Sv. Ivan Rilski" EAD Clinic of clinical hematology, Dpt. of medical oncology	Sofia
Bulgaria	MHAT Serdika EOOD Department of Medical Oncology	Sofia
Bulgaria	Spec. hospital for active treatment of oncology dis. EOOD Department of medical oncology and palliative care	Sofia
Bulgaria	SHAT of oncology diseases Dr. Marko Antonov Markov" EOOD Department of medical oncology and palliative therapy	Varna
Bulgaria	"Complex Ongology Center - Vratsa" EOOD Department of Medical oncology	Vratsa
Czechia	Masarykuv onkologicky ustav Klinika komplexni onkologicke pece	Brno
Czechia	Fakultni nemocnice Ostrava Klinika onkologicka	Ostrava
Czechia	Fakultni nemocnice Olomouc Onkologicka klinika	Praha
Czechia	Thomayerova nemocnice Onkologicka klinika 1. LF UK a TN	Praha
Czechia	Vseobecna fakultni nemocnice Onkologicka klinika VFN a 1. LF UK	Praha
Denmark	Aalborg Universitetshospital, Syd Onkologisk Afdelin	Aalborg
Denmark	Regionshospitalet Herning, Hospitalsenheden Vest Onkologisk Afdeling	Herning
Denmark	Rigshospitalet Onkologisk Klinik	Kobenhavn
Denmark	Odense Universitetshospital Onkologisk Afdeling R	Odense
Estonia	East Tallinn Central Hospital Center of Oncology	Tallinn
Estonia	North Estonia Medical Centre Foundation Oncology and Haematology clinic	Tallinn
Estonia	Tartu University Hospital, Hematology - Oncology clinic, Radiotherapy and oncological therapy	Tartu
France	Institut Sainte Catherine	Avignon
France	CHU Jean Minjoz Service d'oncologie médicale	Besancon
France	CHU Morvan Institut de Cancérologie et d'Hématologie	Brest
France	Hopital Privé Jean Mermoz Service de Gastro entérologie et d'Oncologie médicale	Lyon
France	Hôpital Nord Franche-Comté - Site du Mittan Service d'oncologie médicale	Montbeliard
France	Centre Antoine Lacassagne Dpt d'Oncologie Médicale	Nice
France	Hôpital Européen Georges Pompidou Oncologie Hépatogastroenterologie-oncologie digestive	Paris
France	Hôpital Saint-Antoine Service d'Oncologie Médicale	Paris
France	Hopital Haut-Leveque Hepato-gastroenterologie et oncologie digestive	Pessac
France	CHU Toulouse Rangueil Oncologie médicale digestive	Toulouse
Germany	Onkologische Schwerpunktpraxis Kurfuerstendamm	Berlin
Germany	Lübecker Onkologische Schwerpunktpraxis im Hochschulstadttei	Luebeck
Germany	Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III	Muenchen
Hungary	Del-Pesti Centrumkh-Orsz. Hematologiai es Infektologiai Int. Szent Laszlo Telephely	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly	Budapest
Hungary	Orszagos Onkologiai Intezet "B" Belgyogyaszati-Onkologiai O. Es Klin. Farmakologiai O.	Budapest
Hungary	Semmelweis University Radiology and Oncotherapy Clinic	Budapest
Hungary	Szent Imre Egyetem Oktatokorhaz Klinikai Onkologia	Budapest
Hungary	Uzsoki Utcai Korhaz Onkoradiologiai Osztaly	Budapest
Hungary	Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum Onkologiai Intezet	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz Onkoradiologiai Osztaly	Gyor
Hungary	Bekes Megyei Kozponti Korhaz	Gyula
Hungary	Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont	Kecskemét
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak Onkoradiologiai Osztaly	Nyíregyháza
Hungary	Pecsi Tudomanyegyetem, Klinikai Kozpont Onkoterapias Intezet	Pécs
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kp. Onkoterápiás Klinika	Szeged
Hungary	JNSZ Megyei Hetenyi Geza Korhaz es Rendelointezet Megyei Onkologiai Centrum	Szolnok
Hungary	Markusovsky Egyetemi Oktatokorhaz Onkoradiologiai Osztaly	Szombathely
Hungary	Zala Megyei Korhaz Onkologiai osztaly	Zalaegerszeg
Ireland	Bon Secours Hospital	Cork
Ireland	Cork University Hospital Department of Medical Oncology	Cork
Ireland	The Adelaide and Meath Hospital	Dublin
Italy	Azienda Policlinico Universitaria - Presidio Monserrato Oncologia Medica	Cagliari
Italy	Azienda Socio Sanitaria Territoriale di Cremona ONCOLOGIA	Cremona
Italy	Istituto Nazionale Tumori I.R.C.C.S "Fondazione G. Pascale" Struttura Complessa di Oncologia Medica Addominale	Napoli
Italy	Istituto Oncologico Veneto IOV - IRCCS Unità Operativa Complessa Oncologia Medica 1	Padova
Italy	A.O.U. Pisana-Ospedale Santa Chiara U.O. di Oncologia Medica 2	Pisa
Italy	Ospedale San Carlo U.O. Oncologia Medica	Potenza
Italy	Arcispedale Santa Maria Nuova Unità di Oncologia	Reggio Emilia
Italy	Policlinico Universitario Campus Biomedico UOC di Oncologia Medica	Roma
Italy	Istituto Clinico Humanitas I.R.C.C.S Dipartimento di Oncologia Medica ed Ematologia	Rozzano (mi)
Italy	IRCSS Casa Sollievo della Sofferenza Dipartimento Onco-Ematologia	San Giovanni Rotondo
Italy	Ospedale S. Bortolo -ULSS8 Berica Distretto Est U.O. ONCOLOGIA	Vicenza
Latvia	P. Stradins Clinical University Hospital	Riga
Latvia	Riga East Univerity Hospital Oncology Centre of Latvia	Riga
Lithuania	Hospital of Lithuania Univ of Health Sciences Kauno klinikos Oncology Institute	Kaunas
Lithuania	Oncology Hospital, Branch of Hospital of Lithuanian Uni. of Health Sciences Kauno klinikos	Kaunas
Lithuania	Klaipeda University hospital	Klaipeda
Lithuania	National Cancer Institute	Vilnius
Netherlands	Rijnstate Oncologie	Arnhem
Netherlands	Albert Schweitzer Ziekenhuis Interne Geneeskunde	Dordrecht
Netherlands	Catharina Ziekenhuis Interne Gesneeskunde/Oncologie	Eindhoven
Netherlands	Ikazia Ziekenhuis Oncologie	Rotterdam
Netherlands	ETZ Elisabeth Interne Geneeskunde	Tilburg
Netherlands	Bernhoven Interne Geneeskunde	Uden
Poland	Bialostockie Centrum Onkologii im Marii Curie-Sklodowskiej Oddzial Onkologii Klinicznej im Dr Ewy Pileckiej z pododdzialem Chemioterapii Dziennej	Bialystok
Poland	Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii	Gdansk
Poland	Przychodnia Lekarska "KOMED"	Konin
Poland	M. Kopernika Provincial Hospital Oddzial Chemioterapii Nowotworow	Lódz
Poland	SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii Oddzial Kliniczny Onkologii i Immunoonkologii	Olsztyn
Poland	Opolskie Centrum Onkologii im. Tadeusza Koszarowskiego Oddzial Onkologii Klinicznej	Opole
Poland	Wielkopolskie Centrum Onkologii im Marii Sklodowskiej-Curie Oddzial Chemioterapii	Poznan
Poland	NU-MED Centrum Diagnostyki i Terapii Onkologicznej Tomaszów Mazowiecki II Sp. z o.o., Pododdzial Chemioterapi	Tomaszów Mazowiecki
Portugal	Hospital Garcia de Orta Serviço de Oncologia Médica	Almada
Portugal	Centro Hospitalar e Universitário de Coimbra - CHUC Unidade de Inovação e Desenvolvimento (UID)	Coimbra
Portugal	Centro Hospitalar Lisboa Norte, Hospital de Santa Maria Serviço de Oncologia Médica	Lisboa
Portugal	Hospital Beatriz Ângelo Serviço de oncologia medic	Loures
Portugal	Instituto Português de Oncologia do Porto FG, EPE -IPO Porto Medical Oncology Dept.	Porto
Romania	Institutul Oncologic "Prof Alexandru Trestioreanu" Busuresti Sectia Oncologie Medicala I	Bucuresti
Romania	Spitalul Clinic "Coltea" Sectia Oncologie Medicala	Bucuresti
Romania	Institutul Oncologic "Prof. Dr. I. Chiricuta" Cluj Napoca Oncologie Medicala	Cluj-Napoca
Romania	Centrul de Oncologie Sf Nectarie Oncology Department	Craiova
Romania	S.C Oncolab S.R.L Sectia Oncologie Medicala	Craiova
Romania	Institutul Regional de Oncologie Iasi Clinica de Oncologie Medicala	Iasi
Romania	Spitalul Clinic Judetean de Urgenta Sibiu Sectia Oncologie Medicala	Sibiu
Romania	S.C ONCOMED S.R.L Departament Oncologie Medicala	Timisoara
Russian Federation	Arkhangelsk Clinical Oncology Dispensary chemotherapy department	Arkhangel'sk
Russian Federation	Clinical Oncology Dispensary No.1 Chemotherapy Department	Krasnodar
Russian Federation	Kursk Regional Clinical Oncology Dispensary Oncology Department	Kursk
Russian Federation	Moscow City Oncology Hospital # 62 chemotherapy department	Moscow
Russian Federation	Russian Cancer Research Center n.a. NN Blokhin Clinical Pharmacology and Chemotherapy	Moscow
Russian Federation	University Headache Clinic Outpatient oncology clinic	Moscow
Russian Federation	Omsk Clinical Oncologic Dispensary Chemotherapy	Omsk
Russian Federation	Pyatigorsk Interdistrict Oncology Dispensary Chemotherapy department	Pyatigorsk
Russian Federation	Rostov Research Institute of Oncology Chemotherapy department	Rostov-on-Don
Russian Federation	Regional Clinical Oncology Dispensary	Ryazan'
Russian Federation	National Medical Research Center of Oncology N.N. Petrova	Saint Petersburg
Russian Federation	Saint Petersburg City Oncology Clilnic	Saint Petersburg
Russian Federation	Scientific Centre for Specialized Medical Care (oncological) Chemotherapy	Saint Petersburg
Russian Federation	Multidisciplinary clinic "Reaviz"	Samara
Russian Federation	Oncology Dispensary No.2	Sochi
Russian Federation	State Research Institution of Oncology of Tomsk Chemotherapy	Tomsk
Russian Federation	SBIH of YR "Clinical oncology hospital" chemotherapy department	Yaroslavl
Slovakia	Narodny onkologicky ustav Oddelenie klinickej onkologie	Bratislava
Slovakia	Vychodoslovensky onkologicky ustav Oddelenie klinickej onkologie	Košice
Spain	Hospital General Universitario Alicante Servicio de Oncología	Alicante
Spain	Hospital Germans Trias i Pujol Unidad de Investigación clínica (UIC) ICO-Oncología medica	Badalona
Spain	H. Valle de Hebrón Servicio de Oncología - (VHIR)	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau Oncología Medica	Barcelona
Spain	Hospital Uni. Reina Sofía - Hospital Provincial Departamento de Oncología Médica	Córdoba
Spain	INSTITUTO CATALAN DE ONCOLOGÍA - ICO Oncología Médica	Hospitalet de Llobregat
Spain	H. Clínico San Carlos Servicio de Oncología Médica	Madrid
Spain	H. Universitario La Paz Oncología Médica	Madrid
Spain	HOSPITAL 12 DE OCTUBRE Servicio Oncología Médica	Madrid
Spain	Hospital Universitario Ramón y Cajal, Servicio de Oncologia Médica	Madrid
Spain	Hospital Unviersitario Gregorio Marañon Servicio de Oncología Médica	Madrid
Spain	Hospital Universitario Marqués de Valdecilla Oncología médica	Santander
Spain	H.Virgen Del Rocio	Sevilla
Spain	Hospital Quirónsalud Valencia Servicio de Oncología Médica	Valencia
Spain	Hospital Universitario Miguel Servet Servicio de Oncología	Zaragoza
Sweden	Falu Lasarett Onkologmottagningen	Falun
Sweden	Lanssjukhuset Ryhov Onkologiska kliniken	Jönköping
Sweden	Universitetssjukhuset Orebro	Örebro
Sweden	Karolinska University Hospital, Solna Studiebehandlingsenheten, B8:09	Solna
Sweden	Norrlands Universitetssjukhus Cancercentrum Umea	Umeå
Ukraine	Cherkasy Regional Oncological Dispensary Regional Clinical Oncological Centre	Cherkasy
Ukraine	Dnipro Regional Oncology Dispensary	Dnipro
Ukraine	MI "Dnipropetrovsk City Multi-field Clinical Hospital #4" Department of Oncology	Dnipro
Ukraine	Institute of Medical Radiology of S.P. Grygoryev of AMS UKR	Kharkiv
Ukraine	Kyiv City Clinical Oncology Centre Chemotherapy Department #2	Kyiv
Ukraine	Municipal Institution of Kyiv Regional Council "Kyiv Regional Clinical Hospital", proctology department	Kyiv
Ukraine	National Institute of Cancer Abdominal Oncology Department	Kyiv
Ukraine	Lviv Regional Oncology Center Chemotherapy department	Lviv
Ukraine	Odesa Regional Oncology Dispensary Day patient Department	Odesa
Ukraine	Podillia Regional Oncology Centre Chemotherapy Department	Vinnytsya
Ukraine	Regional Clinical Oncological Dispensary Department of Oncology	Zaporozhye
United Kingdom	Aberdeen Royal Infirmary Oncology Department	Aberdeen
United Kingdom	University Hospitals Bristol Bristol Haematology & Oncology Centre	Bristol
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Leicester Royal Infirmary The HOPE Clinical Trials Unit	Leicester
United Kingdom	Hammersmith Hospital Gary Weston Centre	London
United Kingdom	Imperial Healthcare NHS Trust Charing Cross Hospital	London
United Kingdom	Royal Marsden Hospital Department of Medicine	London
United Kingdom	Sarah Cannon Research Institute UK Clinical Trials	London
United Kingdom	Christie Hospital NHS Foundation Trust GI & Endocrine	Manchester
United Kingdom	Glan Clwyd Hospital North Wales Cancer Treatment Centre	Rhyl
United Kingdom	Royal Marsden Hospital Department of Medicine	Sutton

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Czechia,  Denmark,  Estonia,  France,  Germany,  Hungary,  Ireland,  Italy,  Latvia,  Lithuania,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Time elapsed between the randomization and the date of radiological tumour progression (according to RECIST 1.1) or death from any cause.	Up to 24 months
Secondary	Overall Survival (OS)	Time elapsed between the date of randomization and the date of death due to any cause.	Up to 24 months
Secondary	Overall response rate (ORR)	The proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and using investigator's tumour assessment.	Up to 24 months
Secondary	Disease control rate (DCR)	The proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST 1.1 criteria and using investigator's tumour assessment.	Up to 24 months
Secondary	Duration of response (DoR)	The time from the first documentation of response (CR or PR) to the first documentation of objective tumour progression or death due to any cause, whichever occurs first.	Up to 24 months
Secondary	Time to treatment failure (TTF)	The time from randomization to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.	Up to 24 months

External Links

•   First Lay Summary
•   First Results Summary