Colorectal Cancer MetastaticPhase 2POCHINCT04262687
Chemotherapy and Immunotherapy as Treatment for MSS Metastatic Colorectal Cancer With High Immune Infiltrate
A Phase 2 study testing Capecitabine, Oxaliplatin and Bevacizumab in people with Colorectal Cancer Metastatic and High Immune Infiltrate, run by Federation Francophone de Cancerologie Digestive at 88 sites in France.
Trial summary
About 85% of cases of non-metastatic colorectal cancer (CRC) are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR); which are also called CRC with microsatellite stability (MSS). Other CRC, i.e. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic, High Immune Infiltrate, Microsatellite Stable
- What is being tested?
- Capecitabine, Oxaliplatin and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 88 sitesFrance
- Study dates
- 6 Apr 2021to 30 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- MSS and pMMR metastatic colorectal adenocarcinoma (metachronous or synchronous metastases), histologically proven
- Patients who have had chemotherapy (neo-adjuvant or adjuvant) or radiotherapy (neo-adjuvant or adjuvant) for the treatment of primary tumor or metastatic resected disease R0 can be included if they have a recurrence more than 6 months after the end of this treatment.
- High immune response defined as the immune infiltration scores obtained on the primary tumour (resection of primary tumour containing at least 2 mm of tumour-free margin between the tumour and non-tumour area)
- Unresectable cancer with at least one measurable metastatic target according to RECIST v1.1 criteria
- WHO PS ≤ 1
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- Life expectancy ≥ 3 months
- Adequate haematological function: neutrophils ≥ 1,500 /mm3, platelets ≥ 100,000/mm3, Hb > 9 g/dL
- Adequate liver function: AST/ALT ≤ 5xULN, total bilirubin ≤ 2xULN, alkaline phosphatase. ≤ 5xULN
- Creatinine clearance > 50 mL/min according to the MDRD formula
- Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour
- Patient who is a beneficiary of the social security system
- Information provided to patient and signature of the informed consent form
Who cannot join
- Active infection requiring intravenous antibiotics at day 1 of cycle 1
- Active or untreated central nervous system metastases
- Another concomitant cancer or history of cancer during the last 5 years, except for carcinoma in situ of the uterine cervix or a basal cell or squamous cell skin carcinoma or any other carcinoma in situ considered as cured
- Previous bone marrow allogenic stem cell transplantation or previous organ transplantation
- History of idiopathic pulmonary fibrosis, medicinal product-related pneumonia or proof of active pneumonia or pneumonitis on a chest CT-scan prior to therapy
- HIV infection, active hepatitis B or C infection, active tuberculosis
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- Colorectal cancer with microsatellite instability (dMMR and/or MSI)
- Patient eligible for curative treatment (resection and/or thermal ablation according to the opinion of the local multidisciplinary tumour meeting board)
- Patient with only primary tumour biopsies available or only a sample of a metastasis (no surgical resection of the primary tumour)
- Previous treatment with anti-PD1 or anti-PDL1 or another immunotherapy
- An auto-immune disease which may worsen during treatment with an immune-stimulating agent (patients with type I diabetes, vitiligo, psoriasis, hypo or hyperthyroidism not requiring immunosuppressant therapy are eligible)
- Long-term immunosuppressant therapy (patients requiring corticosteroid therapy are eligible if administration at a dose ≤ 10 mg prednisone equivalent dose per day, administration of steroids by a route of administration resulting in minimal systemic exposure (cutaneous, rectal, ocular or inhalation) is authorised)
- Known severe hypersensitivity to monoclonal antibodies, to one of the medicinal products used or to one of the excipients in the products used or a history of anaphylactic shock or of uncontrolled asthma
- Vaccinations (live vaccine) within 30 days prior to start of treatment
- Dihydropyrimidine Dehydrogenase (DPD) deficiency defined by uracilemy level ≥ 16 ng/mL
- QT/QTc interval > 450 msec in men and > 470 msec in women
- One of the following disorders during the 6 months prior to inclusion: myocardial infarction, unstable/severe angina pectoris, coronary artery bypass grafting, NYHA class II, III or IV congestive heart failure, stroke or transient ischaemic attack
- All uncontrolled progressive disorders during the last 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency, arterial hypertension
- History of an inflammatory digestive disease, obstruction or sub-obstruction not resolved with symptomatic treatment
- Peptic ulcer disease not healed before the treatment
- Not controlled HTA
- Patient already enrolled in another therapeutic trial with an ongoing investigational drug or whose treatment ended less than 4 weeks before inclusion
- Absence of effective contraception in patients (male and/or female patients) of childbearing potential, a pregnant or breastfeeding woman, women of childbearing potential and who have not had a pregnancy test
- Impossibility to submit to medical follow-up of the trial due to geographic, social or psychological reasons
Trial locations and contacts
88 sites in 1 country.
88 sites in 1 country
France88 sites, 88 recruiting
- Not yet recruiting
Ch - Centre Hospitalier D'Abbeville
Abbeville, 80090
Mathieu Pauwels, Dr, 0322255310, pauwels.mathieu@ch-abbeville.fr
Christine PIPROT, Dr, 0322255749, piprot.christine@ch-abbeville.fr
- Recruiting
Chu - Hôpital Sud
Amiens
Vincent HAUTEFEUILLE, Dr, 0322088849, hautefeuille.vincent@chu-amiens.fr
Justine TURPIN, Dr, 0322088849, justineturpin@gmail.com
- Not yet recruiting
Privé - Clinique de L'Europe
Amiens
Michel GOZY, Dr, 0360125344, michel.gozy@cthe-amiens.fr ; secretariat.gozy@cthe-amiens.fr
Khadija KALAI, Dr, 0360127678 ; 0360126343, khadija.kalai@cthe-amiens.fr
- Not yet recruiting
Privé - Ico - Site Paul Papin
Angers, 49055
Judith RAIMBOURG, Dr, 0240679821, judith.raimbourg@ico.unicancer.fr
Olivier Joseph CAPITAIN, Dr, 0241352734, olivier.capitain@ico.unicancer.fr
- Not yet recruiting
Privé - Hôpital Privé Pays de Savoie
Annemasse, 74100
Wulfran CACHEUX, Dr, +33 4 50 83 42 38, w.cacheux@ramsaygds.fr
Laetitia TOUIHRI MAXIMIN, Arc Étude, 0450822675, ltouihrimaximin@ch-alpes-leman.fr
- Recruiting
Privé - Hôpital Privé D'Antony
Antony, 92160
Anne THIROT BIDAULT, Dr, +33 1 46 74 41 73, a.t.bidault@gmail.com
Stanislas ROPERT, Dr, 0158411439, stanislasropert@gmail.com
- Recruiting
Ch - Hôpital Henri Duffaut
Avignon, 84902
Thibault BROTELLE, Dr, +33 4 32 75 93 30, brotelle.thibault@ch-avignon.fr
Olivier BOULAT, Dr, 0432753121 ; 0492759300, oboulat@ch-avignon.fr
- Recruiting
Prive - Institut Du Cancer Avignon Provence
Avignon
Rania BOUSTANY-GRENIER, 0490276262, r.boustany@isc84.org
Laurent MINEUR, 0490276181, l.mineur@isc84.org
- Recruiting
Ch - Centre Hospitalier de La Côte Basque
Bayonne, 64100
Franck AUDEMAR, Dr, +33 5 59 44 37 22, faudemar@ch-cotebasque.fr
Anne GUILNGAR, Dr, +33 5 59 44 37 22, aguilngar@ch-cotebasque.fr
- Not yet recruiting
Privé - Clinique Capio Balharra
Bayonne
Marjorie FAURE, Dr, 0536289002, marjorie.faure@copb.eu
Maciej ROTARSKI, Dr, 0540078415, Maciej.rotarski@copb.eu
- Not yet recruiting
Ch - Centre Hospitalier de Beauvais
Beauvais, 60021
Fayçal HOCINE, Dr, +33 3 44 11 23 09, f.hocine@ch-beauvais.fr ; fayoncologie@yahoo.fr
Fabienne HUYSMAN, Arc Étude, 0344112633, f.huysman@ch-beauvais.fr
- Not yet recruiting
Chu - Hôpital Jean Minjoz
Besançon, 25030
Stéfano KIM, Dr, +33 3 81 98 87 75, alrollin@chu-besancon.fr
Marine JARY, Dr, 0381479999, jary.marine@gmail.com
- Recruiting
Ch - Centre Hospitalier de Béziers
Béziers
Mohamed RAMDANI, Dr, 0467357024, mohamed.ramdani@ch-beziers.fr
Ana PIGUI, Dr, 0467357024, pituitary.ana@infonie.fr
- Recruiting
Privé - Cac - Clinique Bergonié
Bordeaux, 33076
Simon PERNOT, Dr, +33 5 56 33 04 00, simon.pernot@aphp.fr
Dominique BECHADE, Dr, 0556337871, d.bechade@bordeaux.unicancer.fr
- Recruiting
Privé - Polyclinique Bordeaux Nord
Bordeaux, 33077
Cédric LECAILLE, Dr, +33 5 56 69 06 81, lecail@hotmail.com; m.balhadere@hotmail.fr
Iris DEVAURE, Dr, 0556690681, irisdevaure@hotmail.com
- Recruiting
Privé - Clinique Tivoli
Bordeaux
Valérie COCHIN, Dr, 0556690671, v.cochin@tivoli-oncologie.fr
Christophe DEBELLEIX, Dr, 0556394728, c.debelleix@tivoli-oncologie.fr
- Recruiting
Chu - Hôpital Ambroise Paré - Service Anatomie Pathologique
Boulogne
Jean-François EMILE, 01 49 09 57 25, jean-francois.emile@uvsq.fr
Gulian RAULT, gulian.rault@student-cs.fr
- Recruiting
Ch - Hôpital Duchenne
Boulogne-sur-Mer
Vincent BOURGEOIS, Dr, 0321993257 ; 0321993241, vincebourgeois@hotmail.com
Guillaume MARIE, Dr, 0321993023, g.marie@ch-boulogne.fr
- Recruiting
Chu - Hôpital Morvan - Institut de Cancérologie
Brest, 29609
Jean-Philippe METGES, Dr, 02 98 22 33 95, jean-philippe.metges@chu-brest.fr
Hélène SIMON, Dr, 0298223395, helene.simon@chu-brest.fr
- Recruiting
Privé - Clinique Pasteur Lanroze Cfro
Brest
Véronique JESTIN LE TALLEC, Dr, 0298313200, véronique.jestin-letallec@oncologie-brest.fr
Brigitte LUCAS, Dr, 0298313336, brigittelucas@oncologie-brest.fr
- Not yet recruiting
Privé - Centre Maurice Tubiana
Caen, 14000
Emmanuel SEVIN, Dr, +33 2 31 82 84 62, e.sevin@i-l-c.fr
Khadija JALALI, Dr, 0231522000, k-jalali@i-l-c.fr
- Recruiting
Privé - Cac - Centre Francois Baclesse
Caen, 14076
Stéphane CORBINAIS, Dr, +33 2 31 45 40 20, s.corbinais@baclesse.unicancer.fr
Mélanie DOS SANTOS, Dr, 0231455002, m.dossantos@baclesse.unicancer.fr
- Not yet recruiting
Prive - Polyclinique Du Parc Caen
Caen
Emmanuel SEVIN, 0231522000
Khadija JALALI, 0231522000
- Not yet recruiting
Privé - Infirmerie Protestante de Lyon
Caluire-et-Cuire, 69300
Johannes HARTWIG, Dr, +33 4 72 00 71 67, johannes.hartwig@infirmerie-protestante.com
Isabelle PAUCHARD, Dr, 0472007196, l_pauchard@yahoo.fr
- Not yet recruiting
Privé - Médipole de Savoie
Challes-les-Eaux, 73190
Christine REBISCHUNG, Dr, +33 4 79 26 80 61, c.rebischung@medipole-de-savoie.fr
Bertrand ROQUES, Dr, 0479268136, b.roques@medipole-de-savoie.fr
- Recruiting
Privé - Hôpital Privé Paul D'Egine
Champigny-sur-Marne, 94500
Adil CHAFAI EL ALAOUI, Dr, +33 1 49 83 64 05, adil.alaoui@gmail.com
Fadila DEMIL, Dr, +33 1 49 83 64 05, fadoc13@hotmail.com
- Recruiting
Ch - Centre Hospitalier de Cholet
Cholet, 49300
You-Heng LAM, Dr, 02 41 49 66 79, you-heng.lam@ch-cholet.fr
Laura VALLEE, Arc Étude, 02 41 49 69 91, laura.vallee@ch-cholet.fr
- Recruiting
Chu - Hôpital Estaing
Clermont-Ferrand
Caroline PETORIN, Dr, +33 4 73 75 05 08, cpetorin@chu-clermontferrand.fr
Denis PEZET, Dr, +33 4 73 75 04 94, dpezet@chu-clermontferrand.fr
- Not yet recruiting
Ch - Hôpitaux Civils de Colmar
Colmar, 68024
Amalia TOPOLSCKI, Dr, 03 89 12 51 23, gamalia.topolscki@ch-colmar.fr
Marion BOLLIET, Dr, 0389124619, Marion.bolliet@ch-colmar.fr
- Not yet recruiting
Privé - Clinique Saint Come
Compiègne, 60204
Kaïs ALDABBAGH, Dr, +33 3 44 92 43 53, kais.aldabbagh@stcome.com
Baihas DIB, Dr, +33 3 44 92 47 35, baissa.dib@stcome.com
- Recruiting
Privé - Clinique de Flandre
Coudekerque-Branche, 59210
Laurence BOUTAUD DE LA COMBE CHOSSIERE, Dr, +33 3 28 28 14 39, jpwagner@onco-institut-adutreix.org ; jpwagner@iadonco.org
Jean-Philippe WAGNER, Dr, +33 3 28 28 14 39, jpwagner@iadonco.org
- Not yet recruiting
Ch - Ghpso - Site de Creil
Creil, 60100
Elisabeth CAROLA, Dr, 03 44 61 63 03, elisabeth.carola@ghpso.fr
Karthiga CHANDIRAKUMARAN, Arc Étude, 03 44 61 63 15, Karthigyini.Chandirakumaran@ghpso.fr
- Recruiting
Chu - Hôpital Henri Mondor
Créteil, 94000
Isabelle BAUMGAERTNER, Dr, +33 1 49 81 25 76, isabelle.baumgaertner@aphp.fr
Emmanuelle JAN, Dr, 0149813753, Emmanuelle.jan@hmn.aphp.fr
- Not yet recruiting
Ch - Chic de Créteil
Créteil
Isabelle COJEAN-ZELEK, Dr, 0145175210, isabelle.cojean-zelek@chicreteil.fr
Sandrine LACOUR, Dr, 0157022398, sandrine.lacour@chicreteil.fr
- Recruiting
Chu - Hôpital François Mitterrand
Dijon, 21079
Sylvain MANFREDI, Pr, +33 3 80 29 37 50, sylvain.manfredi@chu-dijon.fr
Alice GAGNAIRE, Dr, 0380293750, alice.gagnaire@chu-dijon.fr
- Not yet recruiting
Privé - Cac - Centre Georges-Francois Leclerc
Dijon, 21079
François GHIRINGHELLI, Pr, +33 3 80 73 75 28, fghiringhelli@cgfl.fr
Julie VINCENT, Dr, 0380737528, jvincent@cgfl.fr
- Recruiting
Privé - Polyclinique de Blois - 3Eme Etage
La Chaussée-Saint-Victor, 41260
Philippe LAPLAIGE, Dr, +33 2 54 90 65 57, dr.laplaige@wanadoo.fr
François BARBERIS, Arc Étude, +33 2 54 90 65 59, fbarberis@clinique-blois.com
- Recruiting
Ch - Chd Vendée
La Roche-sur-Yon, 85925
Margot LALY, Dr, +33 2 51 44 61 68, margot.laly@chd-vendee.fr
Paul GIROT, Dr, +33 2 51 44 61 68, paul.girot@chd-vendee.fr
- Recruiting
CH - GROUPE HOSPITALIER DE La Rochelle RE AUNIS
La Rochelle
- Recruiting
Privé - Hôpital Franco Britannique
Levallois-Perret
Benoist CHIBAUDEL, Dr, 0147591924, benoist.chibaudel@ihfb.org
Alexandra BOUAZIZ, Dr, 01 47 59 19 25, alexandra.bouaziz@cognacq-jay.fr
- Not yet recruiting
Privé - Clinique Du Bois
Lille
Eric Yaovi Mesan AMELA, Dr, 03 27 09 10 10, ericamela@yahoo.fr
Rémi TURBE, Arc Étude, 03 20 00 97 57, rturbe@centre-bourgogne.com
- Recruiting
Chu - Centre Hospitalier Dupuytren
Limoges, 87042
Valerie LE BRUN LY, Dr, +33 5 55 05 63 96, valerie.ly@chu-limoges.fr
Frédéric THUILLIER, Dr, 0555056100, frederic.thuillier@chu-limoges.fr
- Recruiting
Ch - Chbs - Hôpital Du Scorff
Lorient, 56322
Joëlle EGRETEAU, Dr, +33 2 97 06 96 94, j.egreteau@ghbs.bzh
Mariella LE SAUX, Arc Étude, +33 2 97 06 96 94, m.lesaux@ch-bretagne-sud.fr
- Recruiting
Privé - Hôpital Jean Mermoz
Lyon, 69008
Chloé VERNET, Dr, +33 4 37 53 87 26, chloe.vernet2@gmail.com
Jérôme DESRAME, Dr, +33 4 37 53 87 26, jerome.desrame@orange.fr
- Recruiting
Privé - Hôpital Saint Joseph
Marseille, 13008
Hervé PERRIER, Dr, +33 4 91 80 82 11, hperrier@hopital-saint-joseph.fr
Christelle BASTHISTE-PELE, Dr, +33 4 91 80 82 03, cbasthiste@hopital-saint-joseph.fr
- Recruiting
Privé - Hôpital Europeen
Marseille, 13331
Yves RINALDI, Dr, +33 4 13 42 77 13, y.rinaldi@hopital-europeen.fr
Julie GIGOUT, Dr, +33 4 13 42 70 00, j.gigout@hopital-europeen.fr
- Not yet recruiting
Chu - Hôpital La Timone
Marseille, 13385
Laétitia DAHAN, Pr, +33 4 91 38 60 23, laetitia.dahan@ap-hm.fr
Muriel DULUC, Dr, +33 4 91 38 60 23, Muriel.duluc@ap-hm.fr
- Recruiting
Privé - Haliodx
Marseille
Isabelle BOQUET
Mélanie GRUBNER, 06 64 58 40 34, melanie.grubner@contractor.haliodx.com
- Recruiting
Ch - Ghi - Groupe Hospitalier de L'Est Francilien - Site de Meaux
Meaux, 77100
Christophe LOCHER, Dr, +33 1 64 35 12 64, c-locher@ch-meaux.fr
Laurence THOMAS MARQUES, Dr, +33 1 45 59 64 76, l-thomas-marques@ch-meaux.fr
- Recruiting
Ch - Hôpital Layné
Mont-de-Marsan, 40 000
Patrick TEXEREAU, Dr, +33 5 58 05 11 66, patrick.texereau@ch-mdm.fr
Morgan ANDRE, Dr, +33 5 58 05 11 64, morgan.andre@live.fr
- Recruiting
Privé - Centre Azureen de Cancerologie
Mougins, 06250
Benjamin HOCH, Dr, +33 4 92 92 37 85, dr.bhoch@gmail.com
Rémy LARGILLIER, Dr, +33 4 92 92 37 39, r.largillier@cac-mougins.fr
- Recruiting
Privé - Hôpital Prive Arnault Tzanck
Mougins, 06250
Benjamin HOCH, Dr, +33 4 92 92 37 37, dr.bhoch@gmail.com
Rémy LARGILLIER, Dr, +33 4 92 92 37 39, r.largillier@cac-mougins.fr
- Not yet recruiting
Privé - Polyclinique de Gentilly
Nancy, 54100
Fabien BROCARD, Dr, +33 3 83 93 50 05, f.brocard@oncog.fr
Laurène GAVOILLE, Dr, +33 3 83 93 50 05, l.gavouille@oncog.fr
- Recruiting
Chu - Hôpital Carémeau
Nîmes, 30029
Valérie PHOUTTHASANG, Dr, +33 4 66 68 31 83, Valivalo@hotmail.com
Yamina BENADJAOUD, Arc Étude, +33 4 66 68 35 28, Yamina.BENADJAOUD@chu-nimes.fr
- Recruiting
Privé - Institut Mutualiste Montsouris
Paris, 75014
Christophe LOUVET, Dr, +33 1 56 61 60 35, christophe.louvet@imm.fr
Emilie SOULARUE, Dr, 0145213720, emilie.soularue@imm.fr
- Recruiting
Chu - Hôpital Europeen Georges Pompidou
Paris, 75015
Julien TAIEB, Dr, +33 1 56 09 35 56, jtaieb75@gmail.com
Claire GALLOIS, Dr, +33 1 56 09 22 97, claire.gallois@aphp.fr
- Recruiting
Privé - Groupe Hospitalier Diaconesses Croix Saint Simon
Paris, 75020
Olivier DUBREUIL, Dr, +33 1 44 74 28 39, ODubreuil@hopital-dcss.org
Antoine ANGELERGUES, Dr, +33 1 44 74 28 39, aangelergues@hopital-dcss.org
- Not yet recruiting
Chu - Hôpital Saint Antoine
Paris
- Not yet recruiting
Chu - Hôpital Saint-Louis
Paris
Thomas APARICIO, Pr, 01 42 49 95 97, thomas.aparicio@aphp.fr
Jean-Marc GORNET, 01 42 49 95 75, jean-marc.gornet@sls.aphp.fr
- Recruiting
Ch - Centre Hospitalier de Pau
Pau, 64046
Juliette THAURY, Dr, +33 5 59 92 49 83, juliette.thaury@ch-pau.fr
Mireille SIMON, Dr, +33 5 59 92 49 83, Mireille.simon@ch-pau.fr
- Recruiting
Privé - Polyclinique Francheville
Périgueux, 24004
Laurent CANY, Dr, +33 5 53 02 13 32, I.cany@oncoradio24.com
Charles-Briac LEVACHE, Dr, +33 5 53 02 13 32, ch.levache@oncoradio24.com
- Recruiting
Ch - Centre Hospitalier Saint-Jean
Perpignan
Faiza KHEMISSA, Dr, +33 4 68 61 61 37, faiza.khemissa@ch-perpignan.fr
Fatima TOUHAMI, Arc Étude, +33 4 68 61 89 01, Fatima.touhami@ch-perpignan.fr
- Not yet recruiting
Chu - Hôpital Haut Lévêque
Pessac
Denis SMITH, 05 57 65 64 39, denis.smith@chu-bordeaux.fr
Éric TERREBONNE, 05 57 65 64 39, eric.terrebonne@chu-bordeaux.fr
- Recruiting
Chu Lyon Sud - Pierre Benite
Pierre-Bénite, 69495
Marion CHAUVENET, Dr, +33 4 78 86 13 02, marion.chauvenet@chu-lyon.fr
Pauline DANION, Dr, +33 4 78 86 13 02, pauline.danion@chu-lyon.fr
- Recruiting
Privé - Centre Cario Hpca
Plérin
- Recruiting
Chu - Centre Hospitalier Universitaire de Poitiers - La Miletrie
Poitiers, 86021
David TOUGERON, Pr, +33 5 49 44 37 51, david.tougeron@chu-poitiers.fr
Camille EVRARD, Dr, 0(49441496, Camille.evrard@chu-poitiers.fr
- Recruiting
Ch - Chic de Quimper
Quimper
Karine BIDEAU, Dr, 0290944117, k.bideau@ch-cornouaille.fr
Pascaline RAMEAU, Arc Étude, 0290264527, p.rameau@ch-cornouaille.fr
- Recruiting
Chu - Centre Hospitalier Universitaire Robert Debre
Reims, 51092
Olivier BOUCHE, Pr, +33 3 26 78 71 72, obouche@chu-reims.fr
Mathilde BRASSEUR, Dr, +33 3 26 78 89 80, mbrasseur@chu-reims.fr
- Recruiting
Privé - Cac - Institut Jean Godinot
Reims, 51726
Damien BOTSEN, Dr, +33 3 26 78 71 70, damien.botsen@reims.unicancer.fr
David BONNERAVE, Arc Étude, 0326504182, david.bonnerave@reims.unicancer.fr
- Recruiting
Chu - Centre Hospitalier Universitaire Pontchaillou
Rennes, 35033
Astrid LIEVRE, Pr, +33 2 99 28 99 72, astrid.lievre@chu-rennes.fr
Astrid LIEVRE, Pr
- Recruiting
Ch - Hôpital Drome Nord
Romans-sur-Isère, 26100
Marie-Claude GOUTTEBEL, Dr, +33 4 75 05 76 59, mc.gouttebel@hopitaux-drome-nord.fr
Marie-Claude GOUTTEBEL, Dr
- Recruiting
Privé - Clinique Saint-Grégoire
Saint-Grégoire
Clément PERRET, Dr, clperret@vivalto-sante.com
Edith CARTON, Dr, 0290094466, ecarton@vivalto-sante.com
- Not yet recruiting
Privé - Cac - Ico - Site René Gauducheau
Saint-Herblain, 44805
Judith RAIMBOURG, Dr, +33 2 40 67 98 21, judith.raimbourg@ico.unicancer.fr
Jean-Luc RAOUL, Dr, 0240679993, jean-lui.raoul@ico.unicancer.fr
- Recruiting
Chu - Centre Hospitalier Universitaire de Saint Etienne - Hôpital Nord - Service Hge
Saint-Priest-en-Jarez, 42270
Jean-Marc PHELIP, Pr, +33 4 77 82 86 19, j.marc.phelip@chu-st-etienne.fr
Amina KHERROUR MEHDI, Dr, +33 4 77 82 86 19, amina.kherrour@chu-st-etienne.fr
- Not yet recruiting
Privé - Polyclinique Saint-Claude
Saint-Quentin, 02100
Pierre VANELSLANDER, Dr, 0323645430, vanelspi@gmail.com
Valérie DEJOUR, Dr, valdejour@hotmail.com
- Not yet recruiting
Privé - Clinique Charcot
Sainte-Foy-lès-Lyon, 69510
Clémence THEVENET, Dr, 04 72 66 67 00, clemence.thevenet@endolyonso.com
Yann MOLIN, Dr, 0472326958, dryannmolin@gmail.com
- Recruiting
Ch - Centre Hospitalier de Saint-Malo
St-Malo, 35403
Anaïs BODERE, Dr, +33 2 99 21 22 64, anais.bodere@gmail.com
Romain DESGRIPPES, Dr, 0299212155 (poste 5307), r.desgrippes@ch-stmalo.fr
- Recruiting
Privé - Clinique Sainte Anne
Strasbourg, 67000
Louis-Marie DOURTHE, Dr, +33 3 88 45 37 50, lm.dourthe@solcrr.org
Anne ESCANDE, Dr, 0388454700, aescande@solrr.org
- Recruiting
Privé - Cac - Paul Strauss / Institut de Cancérologie de Strasbourg Europe
Strasbourg, 67065
Meher BEN ABDELGHANI, Dr, +33 3 88 25 24 85, m.ben-abdelghani@icans.eu
Christine BELLETIER, Dr, +33 3 88 25 24 85, cbelletier@strasbourg.unicancer.fr
- Not yet recruiting
Chu - Hôpital Foch
Suresnes, 92151
May MABRO, Dr, +33 1 46 25 21 68, m.mabro@hopital-foch.org
Asmahane BENMAZIANE TEILLET, Dr, 0146252864, a.benmaziane@hopital-foch.com
- Not yet recruiting
Privé - Polyclinique de L'Ormeau
Tarbes, 65000
Philippe AYELA, Dr, +33 5 62 93 59 29, nathaliemonteiro@wanadoo.fr
Dina Meryem FERHAT, Arc Étude, 0562443345, dina-meryem.ferhat@polyclinique-ormeau.com
- Recruiting
Ch - Hôpital Sainte Musse
Toulon, 83000
Camille SIBERTIN-BLANC, Dr, +33 4 94 14 52 75, camille.sibertin-blanc@ch-toulon.fr
Xavier TCHIKNAVORIAN, Dr, +33 4 94 61 62 21, Xavier.Tchiknavorian@ch-toulon.fr
- Recruiting
Chu - Hôpital Trousseau
Tours, 37044
Thierry LECOMTE, Pr, +33 2 47 47 59 00, thierry.lecomte@univ-tours.fr
Anaïs JAILLAIS, Dr, 0247474747, anaisjaillais@gmail.com
- Not yet recruiting
Ch - Centre Hospitalier de Valenciennes
Valenciennes, 59300
Eduardo BARRASCOUT, Dr, +33 3 27 14 32 05, barrascout-e@ch-valenciennes.fr
Claudiu Pavel CORNEA, Dr, 0607736504, cornea-cp@ch-valenciennes.fr
- Recruiting
Privé - Cac - Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, 54519
Pierre LEHAIR, Dr, +33387818117, pierrelehair@gmail.com
Céline GAVOILLE, Dr, 0383598461, c.gavoille@nancy.unicancer.fr
- Recruiting
Chu - Hôpital Bradois
Vandœuvre-lès-Nancy
Anthony LOPEZ, Dr, 0383157692, a.lopez@chru-nancy.fr
Chloé MARECHAL, Dr, 0383155535, chloe.marechal@hotmail.fr
- Not yet recruiting
Chu - Hôpital Paul Brousse
Villejuif, 94804
Ayhan ULUSAKARYA, Dr, +33 1 45 59 35 70, ayhan.ulusakarya@aphp.fr
Mariem ARFAOUI, Arc Étude, 0145593712, marier.arfaoui@aphp.fr
- Recruiting
Privé - Cac - Institut Gustave Roussy
Villejuif
About this study
Official title: Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study
About 85% of cases of non-metastatic colorectal cancer (CRC) are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR); which are also called CRC with microsatellite stability (MSS). Other CRC, i.e. 15%, are "microsatellite unstable" (MSI) with deficient DNA Mismatch-Repair system (dMMR). These latter are characterised by generation of many neo-antigens, which result in a high anti-tumour immune response and a high peri- and/or intra-tumour lymphocyte infiltration (TIL). Investigators recently showed, with a prospectively validated immune score, that 14% of localised MSS/pMMR CRC are also highly infiltrated by CD3+ lymphocytes. This same immune score has made it possible to measure high lymphocyte infiltration in hepatic metastases, in particular, in patients treated with XELOX/FOLFOX.
Pembrolizumab, an anti-PD1 monoclonal antibody (programmed death-1) is an immune checkpoint inhibitor (ICI) of PD1/PD-L1 axis, recently approved in many cancers. Anti-PD1 antibodies have recently been reported as being very effective in patients with dMMR metastatic CRC (mCRC). In the study by Le DT et al. pMMR mCRC did not seem to benefit from anti-PD1 antibodies. However, it is possible that 20% of pMMR mCRC with a high CD3+ infiltrate in the tumour may be a subgroup of pMMR mCRC sensitive to ICI, as is the case for dMMR mCRC. Lastly, immunogenic cell death induced by chemotherapy, such as oxaliplatin, can increase the efficacy of ICI.
Read more
The prognostic value of lymphocyte infiltrate has been demonstrated in CRC by several teams. However, no validated test is used in routine clinical practice. Previously, investigators described an automated and reproducible method for analysis of TIL and investigators validated it for clinical use. Automated tests evaluating TIL are performed on virtual slides and have showed that, out of 1,220 tumours tested, 20% were highly infiltrated by CD3+ T cells. Patients presenting with a pMMR CRC with a high immune infiltrate had a better progression-free survival (HR=0.70; p=0.02). An immunoscore® described by Galon et al. has also a high prognostic value in CRC and is based on CD3+ and CD8+ T cells infiltration in the center and periphery of the tumour. Finally, approximately 14% of tumours with a high immune infiltrate have been found in patients with metastatic CRC.
Investigators formulated the hypothesis that patients with a pMMR CRC with a high immune infiltrate can be sensitive to ICI . Therefore, blocks of resected primary tumour will be collected and analysed prospectively. For each patient, slides containing tumour tissue and adjacent non-tumour tissue will be analysed using two techniques : immunoscore® and TuLIS score.It consist in Immunohistochemistry with CD3 and CD8 staining. Slides will be scanned and analysed by image analysis as previously described . Tumours will then be classified as having a "high" or "low" immune response according to type of lymphocyte infiltrate, which is independent of pre-analytic conditions. Only patients with a high immune response will be eligible for the POCHI trial. Other biomarkers will be analysed like other immune populations or mutational load. If investigators identify an immune score which seems clinically relevant to predict sensitivity to ICI in pMMR mCRC, this will make it possible to plan a randomised phase III trial comparing chemotherapy and anti-angiogenic antibody versus chemotherapy and anti-angiogenic antibody plus pembrolizumab in patients with a pMMR mCRC with a high immune score and/or a hypermutated genotype.
Investigators choose PFS at 10 months as primary endpoint in POCHI trial because it is a surrogate marker of OS. Actually median PFS in first-line setting with a doublet plus a biological agent is range from 8 to 11 months in unresectable mCRC, corresponding to a PFS of 50% at 10 months. The alternative clinical hypothesis to obtain 70% of patients alive and without progression at 10 months is ambitious and currently not achieved with current chemotherapies plus a biological agent. Up until now there is no data concerning survivals outcomes of patients with a MSS mCRC with high immune infiltration score.
- Being tested
- Capecitabine, Oxaliplatin, Bevacizumab, Pembrolizumab
- Keywords
- immunotherapy, immune infiltrate, first line
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
2000 mg/m²/day, from day 1 to 14 of each cycle
OxaliplatinDrug
130 mg/m² by IV infusion over 2 hours, on day 1 of each cycle
BevacizumabDrug
7.5 mg/kg by IV infusion over 60 minutes, on day 1 of each cycle
PembrolizumabDrug
200 mg by IV infusion over 30 minutes, on day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy + chemotherapy | Experimental | Xelox bevacizumab plus pembrolizumab every 3 weeks up until disease progression, unacceptable toxicity, refusal by the patient, withdrawal of consent, pregnancy or decision by the investigator. Receives: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of patients alive and without progression at 10 months after inclusion
Progression is evaluated by CT scan, according to RECIST criteria (version 1.1) definition by the investigator. Death was also considered as an event (all causes). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed during the study (NADIR), or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 10 months after inclusion
Secondary outcomes (2)
Overall survival
Overall survival is defined as the time from the date of the patient's inclusion to the patient's death (all causes). For alive patients the date of the latest news is taken into account
Measured: Up to 2 years after the end of the treatment
Histological response in case of secondary resection
Response evaluated according to the TRG (Rubbia-Brandt L et al. Annals Oncol 2007), for patients who underwent a secondary resection
Measured: Up to 2 years after the end of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start6 Apr 2021
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federation Francophone de Cancerologie Digestive
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David TOUGERON, MD,PHD, Principal investigator, CHU Poitiers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04262687
- Sponsor's protocol ID
- FFCD 1703 POCHI
- Acronym
- POCHI
- Status last verified
- Aug 2023
- First submitted
- 6 Feb 2020
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Carbonnel F, Soularue E, Coutzac C, Chaput N, Mateus C, Lepage P, Robert C. Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora? Semin Immunopathol. 2017 Apr;39(3):327-331. doi: 10.1007/s00281-016-0613-x. Epub 2017 Jan 16.
PubMed 28093620Caulet M, Lecomte T, Bouche O, Rollin J, Gouilleux-Gruart V, Azzopardi N, Leger J, Borg C, Douillard JY, Manfredi S, Smith D, Capitain O, Ferru A, Moussata D, Terrebone E, Paintaud G, Ternant D. Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients. Clin Pharmacokinet. 2016 Nov;55(11):1381-1394. doi: 10.1007/s40262-016-0406-3.
PubMed 27312193Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012 Jun 28;486(7404):537-40. doi: 10.1038/nature11219.
PubMed 22722843Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012 Mar 15;12(4):298-306. doi: 10.1038/nrc3245.
PubMed 22419253Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.
PubMed 29097493Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, Stalter S, Shak S, Adelman D. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001 Feb 1;19(3):843-50. doi: 10.1200/JCO.2001.19.3.843.
PubMed 11157038Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011.
PubMed 25428504Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D'Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017 May 4;545(7652):60-65. doi: 10.1038/nature22079. Epub 2017 Apr 10.
PubMed 28397821Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, Konieczny BT, Daugherty CZ, Koenig L, Yu K, Sica GL, Sharpe AH, Freeman GJ, Blazar BR, Turka LA, Owonikoko TK, Pillai RN, Ramalingam SS, Araki K, Ahmed R. Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science. 2017 Mar 31;355(6332):1423-1427. doi: 10.1126/science.aaf0683. Epub 2017 Mar 9.
PubMed 28280249Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016 Jun;22(6):598-605. doi: 10.1038/nm.4102. Epub 2016 May 9.
PubMed 27158904Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, Valtorta E, Schiavo R, Buscarino M, Siravegna G, Bencardino K, Cercek A, Chen CT, Veronese S, Zanon C, Sartore-Bianchi A, Gambacorta M, Gallicchio M, Vakiani E, Boscaro V, Medico E, Weiser M, Siena S, Di Nicolantonio F, Solit D, Bardelli A. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012 Jun 28;486(7404):532-6. doi: 10.1038/nature11156.
PubMed 22722830Pauken KE, Wherry EJ. Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 2015 Apr;36(4):265-76. doi: 10.1016/j.it.2015.02.008. Epub 2015 Mar 18.
PubMed 25797516Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium; Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. doi: 10.1038/nature08821.
PubMed 20203603Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragon L, Jacquelot N, Qu B, Ferrere G, Clemenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018 Jan 5;359(6371):91-97. doi: 10.1126/science.aan3706. Epub 2017 Nov 2.
PubMed 29097494Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011 Jun;11(6):426-37. doi: 10.1038/nrc3066. Epub 2011 May 12.
PubMed 21562580
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pembrolizumab in Combination With Xelox Bevacizumab in Patients With Microsatellite Stable Mestatic Colorectal Cancer and a High Immune Infiltrate : a Proof of Concept Study
- ClinicalTrials.gov ID
- NCT04262687
- Acronym / sponsor ID
- POCHI / FFCD 1703 POCHI
- Keywords
- immunotherapy, immune infiltrate, first line
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Federation Francophone de Cancerologie DigestiveUniversity, hospital or other
- Study start
- 6 Apr 2021 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 10 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
About 85% of cases of non-metastatic colorectal cancer (CRC) are related to chromosomal instability and have a proficient DNA Mismatch-Repair system (pMMR); which are also called CRC with microsatellite stability (MSS). Other CRC, i.e. 15%, are "microsatellite unstable" (MSI) with deficient DNA Mismatch-Repair system (dMMR). These latter are characterised by generation of many neo-antigens, which result in a high anti-tumour immune response and a high peri- and/or intra-tumour lymphocyte infiltration (TIL). Investigators recently showed, with a prospectively validated immune score, that 14% of localised MSS/pMMR CRC are also highly infiltrated by CD3+ lymphocytes. This same immune score has made it possible to measure high lymphocyte infiltration in hepatic metastases, in particular, in patients treated with XELOX/FOLFOX.
Pembrolizumab, an anti-PD1 monoclonal antibody (programmed death-1) is an immune checkpoint inhibitor (ICI) of PD1/PD-L1 axis, recently approved in many cancers. Anti-PD1 antibodies have recently been reported as being very effective in patients with dMMR metastatic CRC (mCRC). In the study by Le DT et al. pMMR mCRC did not seem to benefit from anti-PD1 antibodies. However, it is possible that 20% of pMMR mCRC with a high CD3+ infiltrate in the tumour may be a subgroup of pMMR mCRC sensitive to ICI, as is the case for dMMR mCRC. Lastly, immunogenic cell death induced by chemotherapy, such as oxaliplatin, can increase the efficacy of ICI.
The prognostic value of lymphocyte infiltrate has been demonstrated in CRC by several teams. However, no validated test is used in routine clinical practice. Previously, investigators described an automated and reproducible method for analysis of TIL and investigators validated it for clinical use. Automated tests evaluating TIL are performed on virtual slides and have showed that, out of 1,220 tumours tested, 20% were highly infiltrated by CD3+ T cells. Patients presenting with a pMMR CRC with a high immune infiltrate had a better progression-free survival (HR=0.70; p=0.02). An immunoscore® described by Galon et al. has also a high prognostic value in CRC and is based on CD3+ and CD8+ T cells infiltration in the center and periphery of the tumour. Finally, approximately 14% of tumours with a high immune infiltrate have been found in patients with metastatic CRC.
Investigators formulated the hypothesis that patients with a pMMR CRC with a high immune infiltrate can be sensitive to ICI . Therefore, blocks of resected primary tumour will be collected and analysed prospectively. For each patient, slides containing tumour tissue and adjacent non-tumour tissue will be analysed using two techniques : immunoscore® and TuLIS score.It consist in Immunohistochemistry with CD3 and CD8 staining. Slides will be scanned and analysed by image analysis as previously described . Tumours will then be classified as having a "high" or "low" immune response according to type of lymphocyte infiltrate, which is independent of pre-analytic conditions. Only patients with a high immune response will be eligible for the POCHI trial. Other biomarkers will be analysed like other immune populations or mutational load. If investigators identify an immune score which seems clinically relevant to predict sensitivity to ICI in pMMR mCRC, this will make it possible to plan a randomised phase III trial comparing chemotherapy and anti-angiogenic antibody versus chemotherapy and anti-angiogenic antibody plus pembrolizumab in patients with a pMMR mCRC with a high immune score and/or a hypermutated genotype.
Investigators choose PFS at 10 months as primary endpoint in POCHI trial because it is a surrogate marker of OS. Actually median PFS in first-line setting with a doublet plus a biological agent is range from 8 to 11 months in unresectable mCRC, corresponding to a PFS of 50% at 10 months. The alternative clinical hypothesis to obtain 70% of patients alive and without progression at 10 months is ambitious and currently not achieved with current chemotherapies plus a biological agent. Up until now there is no data concerning survivals outcomes of patients with a MSS mCRC with high immune infiltration score.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy + chemotherapy | Experimental | Drug: Capecitabine, Drug: Oxaliplatin, Drug: Bevacizumab, Drug: PembrolizumabXelox bevacizumab plus pembrolizumab every 3 weeks up until disease progression, unacceptable toxicity, refusal by the patient, withdrawal of consent, pregnancy or decision by the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age ≥ 18 years
- MSS and pMMR metastatic colorectal adenocarcinoma (metachronous or synchronous metastases), histologically proven
- Patients who have had chemotherapy (neo-adjuvant or adjuvant) or radiotherapy (neo-adjuvant or adjuvant) for the treatment of primary tumor or metastatic resected disease R0 can be included if they have a recurrence more than 6 months after the end of this treatment.
- High immune response defined as the immune infiltration scores obtained on the primary tumour (resection of primary tumour containing at least 2 mm of tumour-free margin between the tumour and non-tumour area)
- Unresectable cancer with at least one measurable metastatic target according to RECIST v1.1 criteria
Key exclusion criteria (24 listed)
- Active infection requiring intravenous antibiotics at day 1 of cycle 1
- Active or untreated central nervous system metastases
- Another concomitant cancer or history of cancer during the last 5 years, except for carcinoma in situ of the uterine cervix or a basal cell or squamous cell skin carcinoma or any other carcinoma in situ considered as cured
- Previous bone marrow allogenic stem cell transplantation or previous organ transplantation
- History of idiopathic pulmonary fibrosis, medicinal product-related pneumonia or proof of active pneumonia or pneumonitis on a chest CT-scan prior to therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Capecitabine2000 mg/m²/day, from day 1 to 14 of each cycle | Drug | Immunotherapy + chemotherapy |
| Oxaliplatin130 mg/m² by IV infusion over 2 hours, on day 1 of each cycle | Drug | Immunotherapy + chemotherapy |
| Bevacizumab7.5 mg/kg by IV infusion over 60 minutes, on day 1 of each cycle | Drug | Immunotherapy + chemotherapy |
| Pembrolizumab200 mg by IV infusion over 30 minutes, on day 1 of each cycle | Drug | Immunotherapy + chemotherapy |
Primary outcome
The rate of patients alive and without progression at 10 months after inclusion
Time frame: 10 months after inclusion
Progression is evaluated by CT scan, according to RECIST criteria (version 1.1) definition by the investigator. Death was also considered as an event (all causes). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions compared the little sum of diameters observed during the study (NADIR), or a measurable increase in a non-target lesion, or the appearance of new lesions
2 secondary outcomes
Overall survival
Time frame: Up to 2 years after the end of the treatment
Histological response in case of secondary resection
Time frame: Up to 2 years after the end of the treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
- Background: PubMed 28093620Carbonnel F, Soularue E, Coutzac C, Chaput N, Mateus C, Lepage P, Robert C. Inflammatory bowel disease and cancer response due to anti-CTLA-4: is it in the flora? Semin Immunopathol. 2017 Apr;39(3):327-331. doi: 10.1007/s00281-016-0613-x. Epub 2017 Jan 16.
- Background: PubMed 27312193Caulet M, Lecomte T, Bouche O, Rollin J, Gouilleux-Gruart V, Azzopardi N, Leger J, Borg C, Douillard JY, Manfredi S, Smith D, Capitain O, Ferru A, Moussata D, Terrebone E, Paintaud G, Ternant D. Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients. Clin Pharmacokinet. 2016 Nov;55(11):1381-1394. doi: 10.1007/s40262-016-0406-3.
- Background: PubMed 22722843Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012 Jun 28;486(7404):537-40. doi: 10.1038/nature11219.
- Background: PubMed 22419253Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012 Mar 15;12(4):298-306. doi: 10.1038/nrc3245.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David TOUGERON, MD,PHD principal investigator
CHU Poitiers
88 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capecitabine, Oxaliplatin and Bevacizumab in people with Colorectal Cancer Metastatic and High Immune Infiltrate, run by Federation Francophone de Cancerologie Digestive at 88 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 88 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jeremie BEZ (0380393483, jeremie.bez@u-bourgogne.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of patients alive and without progression at 10 months after inclusion (time frame: 10 months after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04262687, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023.