Standard Chemotherapy vs Immunotherapie in 2nd Line Treatment of MSI Colorectal Mestastatic Cancer
NCT ID: NCT03186326
Last Updated: 2025-06-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
132 participants
INTERVENTIONAL
2018-04-24
2025-03-01
Brief Summary
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Preliminary results suggest that patients with MSI mCRC are highly sensitive to ICI even chemoresistant tumors receiving several lines of chemotherapy. Recently, another anti-PD1 alone or in combination with an anti-CTLA4 (antigen associated with cytotoxic T-lymphocyte 4) was tested in the MSI CRCs and a selection of interesting results in heavily pretreated patients with a disease control rate of 56% for monotherapy and 81% for combinated therapy.
Anti-PD1s now have marketing authorization for patients with melanoma and metastatic pulmonary carcinoma , Which are known to have a high level of mutations . ICIs appear to be as promising in MSI CRCs as in other tumors and therefore face the same major challenges.
Avalumab is an anti-PD-L1 antibody recently tested in several different types of tumors with promising results and is currently being studied in phase III in gastric cancer. There is no data on the effectiveness of this ICI in the MSI mCRCs. In addition, only anti-PD1 was used in the MSI-mCRC and not the anti-PD-L1, and only in chemoresistance (3rd line or more). The main objective of the SAMCO study is to test the efficacy and tolerance of avelumab in the 2nd line of treatment in patients with a MSI mCRC progression after standard 1st line chemotherapy +/- targeted therapy.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A Chemotherapy (standard treatment)
FOLFOX or FOLFIRI +/- targeted therapy
FOLFOX regimen
A course of treatment every 14 days
Oxaliplatin: 85 mg/m² IV over 2 hours Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine) IV over 2 hours 5FU bolus: 400 mg/m² IV bolus over 10 minutes in 100 ml 0.9% NaCl 5FU continuous: 2,400 mg/m² in NaCl 0.9% in IV over 46 hours
FOLFIRI Protocol
A course of treatment every 14 days
Irinotecan: 180 mg/m² IV over 1H30 Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine) IV over 2 hours 5FU bolus: 400 mg/m² IV bolus over 10 minutes in 100 ml 0.9% NaCl 5FU continuous: 2,400 mg/m² in NaCl 0.9% in IV over 46 hours
Panitumumab
Administered at 6 mg/Kg
Cetuximab
Administered at 500 mg/m²
Bevacizumab
Administered at 5 mg/Kg
Aflibercept
Administered at 4 mg/Kg
Arm B - Immunotherapy (experimental arm)
Avelumab
Avelumab
A course of treatment every 14 days. Premedication obligatory with antihistamines and paracetamol (example: 25-50 mg diphenhydramine and 500-650 mg paracetamol) IV, approximately 30 to 60 minutes before each dose of avelumab.
Then:
Avelumab: 10 mg/kg IV in 1 hour diluted with 0.9% saline solution; alternatively a 0.45% saline solution can be used if needed
Interventions
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FOLFOX regimen
A course of treatment every 14 days
Oxaliplatin: 85 mg/m² IV over 2 hours Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine) IV over 2 hours 5FU bolus: 400 mg/m² IV bolus over 10 minutes in 100 ml 0.9% NaCl 5FU continuous: 2,400 mg/m² in NaCl 0.9% in IV over 46 hours
FOLFIRI Protocol
A course of treatment every 14 days
Irinotecan: 180 mg/m² IV over 1H30 Folinic acid: 400 mg/m² (or 200 mg/m² if Elvorine) IV over 2 hours 5FU bolus: 400 mg/m² IV bolus over 10 minutes in 100 ml 0.9% NaCl 5FU continuous: 2,400 mg/m² in NaCl 0.9% in IV over 46 hours
Avelumab
A course of treatment every 14 days. Premedication obligatory with antihistamines and paracetamol (example: 25-50 mg diphenhydramine and 500-650 mg paracetamol) IV, approximately 30 to 60 minutes before each dose of avelumab.
Then:
Avelumab: 10 mg/kg IV in 1 hour diluted with 0.9% saline solution; alternatively a 0.45% saline solution can be used if needed
Panitumumab
Administered at 6 mg/Kg
Cetuximab
Administered at 500 mg/m²
Bevacizumab
Administered at 5 mg/Kg
Aflibercept
Administered at 4 mg/Kg
Eligibility Criteria
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Inclusion Criteria
* MSI-H determined by immunohistochemistry (loss of expression of MLH1, MSH2, MSH6 and/or PMS2) or by molecular biology
* At least one measurable target (primary tumor or metastasis) according to RECIST v1.1
* Mutational status RAS and BRAF
* Age ≥ 18
* OMS ≤ 2
* Life expectancy \< 3 months
* Patient failure (progression or unacceptable toxicity) of chemotherapy containing fluoropyrimidine (capecitabine or 5FU) +/- irinotecan +/- oxaliplatin with or without cetuximab, bevacizumab and panitumumab (patients in progression during or within 3 months after discontinuation of adjuvant chemotherapy are eligible)
* PNN \> 1500/mm3, platelets \> 100 000/mm3, Hb \> 9 g/dL
* Total bilirubin \< 25 µmol/L, ASAT \< 5x LSN, ALAT \< 5 x LSN, PT \> 60%, , PAL\<2.5 x LSN ( \< 5 x LSN in case of hepatic metastasis)
* Creatinine clearance \> 50 ml/min according to MDRD formula (≥ 30 ml/min according to the Cockcroft-Gault formula)
* Patient belonging to a social security scheme
* Patient information and signature of the informed consent
Exclusion Criteria
* Patient treated with FOLFIRINOX or FOLFOXIRI in 1st line
* Cerebral metastasis
* Previous treatment with anti-PD1 or anti-PDL1
* Autoimmune disease that might be aggravated during treatment with an immuno-stimulating agent (patients with type I diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible)
* Immunosuppressive long-term treatment (patients necessitating a corticotherapy are eligible if they are administered in doses \< or = to the equivalent of 10 mg of prednisone daily, administration of steroids by a route resulting in minimal systemic exposure (local, intra-anal, intraocular or inhalation) are eligible).
* Transplant patients (including stem cell transplants), HIV positive or other immune deficiency syndromes
* Active infection by HBV or HCV
* Known severe hypersensitivity to monoclonal antibodies or history of anaphylactic shock, or uncontrolled asthma
* Any known specific contraindication or allergy to the treatments used in the study
* Persistence of toxicities related to 1st line chemotherapy grade \> 2 (NCI-CTC v4.0) (except alopecia and neuropathy sequelae of oxaliplatin)
* Vaccination during the 4 weeks preceding the start of treatment
* Known deficit in DPD
* QT/QTc interval \> 450 msec for men and \> 470 msec for women
* K+ \< LIN, Mg2+ \< LIN, Ca2+ \< LIN
* Following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischemic attack
* Any progressive pathology not stabilised over the past 6 months: hepatic failure, renal failure, respiratory failure
* Patient with interstitial pneumonitis or pulmonary fibrosis
* History of chronic diarrhea or inflammatory disease of the colon or rectum, or unresolved occlusion or sub-occlusion in symptomatic treatment
* History of malignant pathologies during the past 5 years except basocellular skin carcinoma or in situ cervical carcinoma, properly treated
* Patient already included in another clinical trial during treatment with an experimental molecule for L2
* Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test
* Persons deprived of liberty or under supervision
* Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons
18 Years
ALL
No
Sponsors
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Federation Francophone de Cancerologie Digestive
OTHER
Responsible Party
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Principal Investigators
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Julien Taieb, Pr
Role: PRINCIPAL_INVESTIGATOR
HOPITAL EUROPEEN G. POMPIDOU
Locations
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Ch - Centre Hospitalier D'Abbeville
Abbeville, , France
Ch - Centre Hospitalier Du Pays D'Aix
Aix-en-Provence, , France
Chu - Hôpital Sud - Service D'Hge
Amiens, , France
Privé - Clinique de L'Europe
Amiens, , France
Cac - Ico Site Paul Papin
Angers, , France
CHU - Hôtel Dieu
Angers, , France
Privé - Hopital Privé D'Antony
Antony, , France
Ch - Hôpital Victor Dupouy
Argenteuil, , France
Ch - Centre Hospitalier Ardeche Meridionale
Aubenas, , France
Ch - Ght Unyon Auxerre
Auxerre, , France
Ch - Hôpital Henri Duffaut
Avignon, , France
Privé - Institut Sainte Catherine
Avignon, , France
Ch - Centre Hôspitalier Côte Basque
Bayonne, , France
Ch - Centre Hospitalier de Beauvais
Beauvais, , France
Chu - Jean Minjoz
Besançon, , France
Privé - Centre de Radiotherapie Pierre Curie
Beuvry, , France
Privé - Polyclinique Bordeaux Nord
Bordeaux, , France
Privé - Cac Institut Bergionié
Bordeaux, , France
Privé - Polyclinique Saint-Privat
Boujan-sur-Libron, , France
Ch - Hôpital Duchenne
Boulogne-sur-Mer, , France
Privé - Clinique Pasteur Lanroze Cfro
Brest, , France
Privé - Centre Maurice Tubiana
Caen, , France
Privé - Cac Centre Francois Baclesse
Caen, , France
Privé - Infirmerie Protestante de Lyon
Caluire-et-Cuire, , France
Ch - Centre Hospitalier de Carcassonne
Carcassonne, , France
Chi - Centre Hospitalier de Castres Mazamet
Castres, , France
Ch - Centre Hospitalier William Morey
Chalon-sur-Saône, , France
Privé - Hopital Prive Sainte Marie
Chalon-sur-Saône, , France
Ch - Centre Hospitalier Metropole Savoie
Chambéry, , France
Ch - Centre Hospitalier de Charleville Mezieres
Charleville, , France
Ch - Centre Hospitalier General
Châlons-en-Champagne, , France
Ch - Centre Hospitalier de Châteauroux
Châteauroux, , France
Ch - Centre Hospitalier de Cholet
Cholet, , France
Ch - Hopitaux Civils de Colmar
Colmar, , France
Privé - Clinique Saint Come
Compiègne, , France
Ch - Centre Hospitalier Sud Francilien
Corbeil-Essonnes, , France
Privé - Clinique Des Cèdres
Cornebarrieu, , France
Privé - Clinique de Flandre
Coudekerque-Branche, , France
Ch - Ghpso Site de Creil
Creil, , France
Ch - Chic de Créteil
Créteil, , France
Chu - Aphp - Hopital Henri Mondor
Créteil, , France
Privé - Institut de Cancerologie de Bourgogne Grrecc
Dijon, , France
Chu - Hopital Francois Mitterrand
Dijon, , France
Privé - Cac- Centre Georges-Francois Leclerc
Dijon, , France
Privé - Ghm Institut Daniel Hollard
Grenoble, , France
Chu - Grenoble Alpes
Grenoble, , France
Privé - Clinique Sainte Marguerite
Hyères, , France
Ch - Centre Hospitalier Marne La Vallee-Jossigny
Jossigny, , France
Chd - Centre Hospitalier Vendee
La Roche-sur-Yon, , France
Privé - Clinique Du Cap D'Or
La Seyne-sur-Mer, , France
Ch - Hopital Andre Mignot
Le Chesnay, , France
Ch - Hopital Louis Pasteur - Oncologie Hematologie
Le Coudray, , France
Privé - Cmc Les Ormeaux
Le Havre, , France
Chu - Aphp - Hôpital de Bicêtre
Le Kremlin-Bicêtre, , France
Ch - Centre Hospitalier Du Mans
Le Mans, , France
Ch - Centre Hospitalier Docteur Schaffner
Lens, , France
Ch - Hôpital Franco Britannique
Levallois-Perret, , France
Privé - Cac - Centre Oscar Lambret
Lille, , France
Chu - Dupuytren
Limoges, , France
Ch - Gh Nord Essone
Longjumeau, , France
Chu - Hôpital de La Croix Rousse
Lyon, , France
Privé - Cac Centre Léon Berard
Lyon, , France
Chu - Hôpital Edouard Herriot
Lyon, , France
Privé - Cac Institut Paoli Calmettes
Marseille, , France
Ch - Hôpital Saint Joseph
Marseille, , France
Privé - Hôpital Européen Marseille
Marseille, , France
Chu - La Timone
Marseille, , France
Ch - Ghi de L'Est Francilien Site de Meaux
Meaux, , France
Ch - Hôpital Belle Isle
Metz, , France
Privé - Clinique Claude Bernard
Metz, , France
Ch - Hôpital Layné
Mont-de-Marsan, , France
Ch - Centre Hospitalier de Montceau Les Mines
Montceau-les-Mines, , France
Ch - Centre Hospitalier de Montélimar
Montélimar, , France
Ch - Groupe Hospitalier Intercommunal Le Raincy
Montfermeil, , France
Privé - Centre de Cancérologie Du Grand Montpellier
Montpellier, , France
Privé - Hôpital Prive Du Confluent Sas
Nantes, , France
Privé - Cac - Centre Antoine Lacassagne
Nice, , France
Chu - Hôpital Caremeau
Nîmes, , France
Chr - Centre Hospitalier Régional de La Source
Orléans, , France
Privé - Cac - Institut Curie
Paris, , France
Chu - Hôpital Cochin
Paris, , France
Chu - Hôpital Europeen Georges Pompidou
Paris, , France
Chu - Aphp - Hôpital Saint Louis
Paris, , France
Chu - Hôpital Saint Antoine
Paris, , France
Chu - Aphp - Gh La Pitié Salpêtrière
Paris, , France
Ch - Centre Hospitalier de Pau
Pau, , France
Ch - Hôpital Saint Jean
Perpignan, , France
Chu - Hôpital Haut Lévêque
Pessac, , France
Privé - Polyclinique Francheville
Périgueux, , France
Ch - Hôpital Lyon Sud
Pierre-Bénite, , France
Privé - Centre Cario - Hcpa
Plérin, , France
Chu - Hôpital de La Miletrie
Poitiers, , France
Ch - Hôpital Rene Dubos
Pontoise, , France
Ch - Hôpital Annecy Genevois
Pringy, , France
Ch - Chic - Centre Hospitalier de Cornouaille
Quimper, , France
Chu - Hôpital Robert Debre
Reims, , France
Chu - Centre Hospitalier Universitaire Pontchaillou
Rennes, , France
Privé - Centre de Radiotherapie Et D'Oncologie Médicale de L'Essone
Ris-Orangis, , France
Privé - Clinique Pasteur
Ris-Orangis, , France
Ch - Hôpitaux Drome Nord
Romans-sur-Isère, , France
Chu - Hôpital Charles Nicolle
Rouen, , France
Privé - Hôpital Privé Saint Gregoire
Saint-Grégoire, , France
Privé - Clinique de L'Union
Saint-Jean, , France
Privé - Cmco Côte D'Opale
Saint-Martin-Boulogne, , France
Privé - Clinique Mutualiste de L'Estuaire - Cite Sanitaire
Saint-Nazaire, , France
Chu - Hôpital Nord - Saint-Étienne
Saint-Priest-en-Jarez, , France
Privé - Clinique Trenel
Sainte-Colombe, , France
Ch - Centre Hospitalier de Soisson
Soissons, , France
Ch - Centre Hospitalier de Saint-Malo
St-Malo, , France
Privé - Cac - Institut de Cancérologie de Strasbourg Europe
Strasbourg, , France
Privé - Clinique Sainte Anne
Strasbourg, , France
Ch - Hopitaux Du Leman
Thonon-les-Bains, , France
Ch - Hôpital Sainte Musse
Toulon, , France
Chu - Hôpital Rangueil
Toulouse, , France
Chu - Hôpital Trousseau
Tours, , France
Chu - Hôpital Nancy-Brabois
Vandœuvre-lès-Nancy, , France
Privé - Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, , France
Chu - Aphp - Hôpital Paul Brousse
Villejuif, , France
Privé - Cac - Gustave Roussy
Villejuif, , France
Ch - Centre Hospitalier Intercommunal
Villeneuve-Saint-Georges, , France
Countries
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References
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Taieb J, Andre T, El Hajbi F, Barbier E, Toullec C, Kim S, Bouche O, Di Fiore F, Chauvenet M, Perrier H, Evesque L, Laurent-Puig P, Emile JF, Bez J, Lepage C, Tougeron D. Avelumab versus standard second line treatment chemotherapy in metastatic colorectal cancer patients with microsatellite instability: The SAMCO-PRODIGE 54 randomised phase II trial. Dig Liver Dis. 2021 Mar;53(3):318-323. doi: 10.1016/j.dld.2020.11.031. Epub 2020 Dec 25.
Taieb J, Sullo FG, Lecanu A, Bourreau C, Barbier E, Gandini A, Bez J, Mulot C, Di Fiore F, Elhajbi F, Borg C, Bouche O, Aparicio T, Zaanan A, Andre T, Tougeron D, Taly V, Laurent-Puig P. Early ctDNA and Survival in Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors: A Secondary Analysis of the SAMCO-PRODIGE 54 Randomized Clinical Trial. JAMA Oncol. 2025 Aug 1;11(8):874-882. doi: 10.1001/jamaoncol.2025.1646.
Taieb J, Bouche O, Andre T, Le Malicot K, Laurent-Puig P, Bez J, Toullec C, Borg C, Randrian V, Evesque L, Corbinais S, Perrier H, Buecher B, Di Fiore F, Gallois C, Emile JF, Lepage C, Elhajbi F, Tougeron D; SAMCO-PRODIGE 54 Investigators. Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability: A Randomized Clinical Trial. JAMA Oncol. 2023 Oct 1;9(10):1356-1363. doi: 10.1001/jamaoncol.2023.2761.
Other Identifiers
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PRODIGE 54 - FFCD 1603
Identifier Type: -
Identifier Source: org_study_id
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