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Metastatic Colorectal CancerPhase 2SAMCONCT03186326

Standard Chemotherapy vs Immunotherapie in 2nd Line Treatment of MSI Colorectal Mestastatic Cancer

A Phase 2 study testing FOLFOX regimen, FOLFIRI Protocol and Avelumab in people with Metastatic Colorectal Cancer and MSI, run by Federation Francophone de Cancerologie Digestive at 120 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Immune chekpoints (ICI) are evaluated in many digestive cancers. Certain types of cancer appear to be rather refractory to ICI such as colorectal cancers (CRC). However, the MSI CRC representing approximately 15% of the CRCs exhibits a high mutational load which generates many potentially immunogenic neoantigens. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer, MSI
What is being tested?
FOLFOX regimen, FOLFIRI Protocol and Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
132 participants
Where
120 sitesFrance
Study dates
24 Apr 2018to 1 Mar 2025
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

  • Histologically proven colorectal adenocarcinoma with metastasis(es) non-resectable
  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • Patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in CPR
  • 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).
Show all 24Show fewer
  • 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

Trial locations and contacts

120 sites in 1 country.

120 sites in 1 country

France120 sites

  • Ch - Centre Hospitalier D'Abbeville

    Abbeville, 80142

  • Ch - Centre Hospitalier Du Pays D'Aix

    Aix-en-Provence, 13616

  • Chu - Hôpital Sud - Service D'Hge

    Amiens, 80054

  • Privé - Clinique de L'Europe

    Amiens, 80090

  • Cac - Ico Site Paul Papin

    Angers, 49055

  • CHU - Hôtel Dieu

    Angers, 49933

  • Privé - Hopital Privé D'Antony

    Antony, 92166

  • Ch - Hôpital Victor Dupouy

    Argenteuil, 95100

  • Ch - Centre Hospitalier Ardeche Meridionale

    Aubenas, 07205

  • Ch - Ght Unyon Auxerre

    Auxerre, 89000

  • Ch - Hôpital Henri Duffaut

    Avignon, 84000

  • Privé - Institut Sainte Catherine

    Avignon, 84918

  • Ch - Centre Hôspitalier Côte Basque

    Bayonne, 64109

  • Ch - Centre Hospitalier de Beauvais

    Beauvais, 60021

  • Chu - Jean Minjoz

    Besançon, 25030

  • Privé - Centre de Radiotherapie Pierre Curie

    Beuvry, 62660

  • Privé - Polyclinique Bordeaux Nord

    Bordeaux, 33000

  • Privé - Cac Institut Bergionié

    Bordeaux, 33076

  • Privé - Polyclinique Saint-Privat

    Boujan-sur-Libron, 34760

  • Ch - Hôpital Duchenne

    Boulogne-sur-Mer, 62321

  • Privé - Clinique Pasteur Lanroze Cfro

    Brest, 29200

  • Privé - Centre Maurice Tubiana

    Caen, 14052

  • Privé - Cac Centre Francois Baclesse

    Caen, 14076

  • Privé - Infirmerie Protestante de Lyon

    Caluire-et-Cuire, 69300

  • Ch - Centre Hospitalier de Carcassonne

    Carcassonne, 11000

  • Chi - Centre Hospitalier de Castres Mazamet

    Castres, 81090

  • Ch - Centre Hospitalier William Morey

    Chalon-sur-Saône, 7100

  • Privé - Hopital Prive Sainte Marie

    Chalon-sur-Saône, 71100

  • Ch - Centre Hospitalier General

    Châlons-en-Champagne, 51005

  • Ch - Centre Hospitalier Metropole Savoie

    Chambéry, 73011

  • Ch - Centre Hospitalier de Charleville Mezieres

    Charleville, 08000

  • Ch - Centre Hospitalier de Châteauroux

    Châteauroux, 36000

  • Ch - Centre Hospitalier de Cholet

    Cholet, 49300

  • Ch - Hopitaux Civils de Colmar

    Colmar, 68024

  • Privé - Clinique Saint Come

    Compiègne, 60204

  • Ch - Centre Hospitalier Sud Francilien

    Corbeil-Essonnes, 91106

  • Privé - Clinique Des Cèdres

    Cornebarrieu, 31700

  • Privé - Clinique de Flandre

    Coudekerque-Branche, 59210

  • Ch - Ghpso Site de Creil

    Creil, 60100

  • Ch - Chic de Créteil

    Créteil, 94000

  • Chu - Aphp - Hopital Henri Mondor

    Créteil, 94000

  • Privé - Institut de Cancerologie de Bourgogne Grrecc

    Dijon, 21000

  • Chu - Hopital Francois Mitterrand

    Dijon, 21079

  • Privé - Cac- Centre Georges-Francois Leclerc

    Dijon, 21079

  • Privé - Ghm Institut Daniel Hollard

    Grenoble, 38028

  • Chu - Grenoble Alpes

    Grenoble

  • Privé - Clinique Sainte Marguerite

    Hyères, 83400

  • Ch - Centre Hospitalier Marne La Vallee-Jossigny

    Jossigny, 77600

  • Chd - Centre Hospitalier Vendee

    La Roche-sur-Yon, 85925

  • Privé - Clinique Du Cap D'Or

    La Seyne-sur-Mer, 83500

  • Ch - Hopital Andre Mignot

    Le Chesnay, 78157

  • Ch - Hopital Louis Pasteur - Oncologie Hematologie

    Le Coudray, 28630

  • Privé - Cmc Les Ormeaux

    Le Havre, 76600

  • Chu - Aphp - Hôpital de Bicêtre

    Le Kremlin-Bicêtre, 94270

  • Ch - Centre Hospitalier Du Mans

    Le Mans, 72037

  • Ch - Centre Hospitalier Docteur Schaffner

    Lens

  • Ch - Hôpital Franco Britannique

    Levallois-Perret, 92300

  • Privé - Cac - Centre Oscar Lambret

    Lille, 59000

  • Chu - Dupuytren

    Limoges, 87042

  • Ch - Gh Nord Essone

    Longjumeau, 91160

  • Chu - Hôpital de La Croix Rousse

    Lyon, 69317

  • Privé - Cac Centre Léon Berard

    Lyon, 69373

  • Chu - Hôpital Edouard Herriot

    Lyon, 69437

  • Privé - Cac Institut Paoli Calmettes

    Marseille, 13273

  • Ch - Hôpital Saint Joseph

    Marseille, 13285

  • Privé - Hôpital Européen Marseille

    Marseille, 13331

  • Chu - La Timone

    Marseille, 13385

  • Ch - Ghi de L'Est Francilien Site de Meaux

    Meaux, 77100

  • Ch - Hôpital Belle Isle

    Metz, 57000

  • Privé - Clinique Claude Bernard

    Metz, 57070

  • Ch - Hôpital Layné

    Mont-de-Marsan, 40024

  • Ch - Centre Hospitalier de Montceau Les Mines

    Montceau-les-Mines, 71300

  • Ch - Centre Hospitalier de Montélimar

    Montélimar, 26216

  • Ch - Groupe Hospitalier Intercommunal Le Raincy

    Montfermeil, 93370

  • Privé - Centre de Cancérologie Du Grand Montpellier

    Montpellier, 34070

  • Privé - Hôpital Prive Du Confluent Sas

    Nantes, 44577

  • Privé - Cac - Centre Antoine Lacassagne

    Nice, 06000

  • Chu - Hôpital Caremeau

    Nîmes, 30000

  • Chr - Centre Hospitalier Régional de La Source

    Orléans, 45067

  • Privé - Cac - Institut Curie

    Paris, 75005

  • Chu - Hôpital Cochin

    Paris, 75014

  • Chu - Hôpital Europeen Georges Pompidou

    Paris, 75015

  • Chu - Aphp - Hôpital Saint Louis

    Paris, 75475

  • Chu - Hôpital Saint Antoine

    Paris, 75571

  • Chu - Aphp - Gh La Pitié Salpêtrière

    Paris, 75651

  • Ch - Centre Hospitalier de Pau

    Pau, 64046

  • Privé - Polyclinique Francheville

    Périgueux, 24000

  • Ch - Hôpital Saint Jean

    Perpignan, 66046

  • Chu - Hôpital Haut Lévêque

    Pessac, 33604

  • Ch - Hôpital Lyon Sud

    Pierre-Bénite, 69310

  • Privé - Centre Cario - Hcpa

    Plérin, 22190

  • Chu - Hôpital de La Miletrie

    Poitiers, 86021

  • Ch - Hôpital Rene Dubos

    Pontoise, 95300

  • Ch - Hôpital Annecy Genevois

    Pringy, 74374

  • Ch - Chic - Centre Hospitalier de Cornouaille

    Quimper, 29000

  • Chu - Hôpital Robert Debre

    Reims, 51092

  • Chu - Centre Hospitalier Universitaire Pontchaillou

    Rennes, 35000

  • Privé - Centre de Radiotherapie Et D'Oncologie Médicale de L'Essone

    Ris-Orangis, 91130

  • Privé - Clinique Pasteur

    Ris-Orangis, 91130

  • Ch - Hôpitaux Drome Nord

    Romans-sur-Isère, 26100

  • Chu - Hôpital Charles Nicolle

    Rouen, 76031

  • Privé - Hôpital Privé Saint Gregoire

    Saint-Grégoire, 35768

  • Privé - Clinique de L'Union

    Saint-Jean, 31240

  • Privé - Cmco Côte D'Opale

    Saint-Martin-Boulogne, 62280

  • Privé - Clinique Mutualiste de L'Estuaire - Cite Sanitaire

    Saint-Nazaire, 44600

  • Chu - Hôpital Nord - Saint-Étienne

    Saint-Priest-en-Jarez, 42270

  • Privé - Clinique Trenel

    Sainte-Colombe

  • Ch - Centre Hospitalier de Soisson

    Soissons, 02209

  • Ch - Centre Hospitalier de Saint-Malo

    St-Malo, 35400

  • Privé - Cac - Institut de Cancérologie de Strasbourg Europe

    Strasbourg

  • Privé - Clinique Sainte Anne

    Strasbourg

  • Ch - Hopitaux Du Leman

    Thonon-les-Bains, 74203

  • Ch - Hôpital Sainte Musse

    Toulon, 83000

  • Chu - Hôpital Rangueil

    Toulouse, 31000

  • Chu - Hôpital Trousseau

    Tours, 37044

  • Chu - Hôpital Nancy-Brabois

    Vandœuvre-lès-Nancy, 54511

  • Privé - Institut de Cancerologie de Lorraine

    Vandœuvre-lès-Nancy, 54519

  • Chu - Aphp - Hôpital Paul Brousse

    Villejuif, 94800

  • Privé - Cac - Gustave Roussy

    Villejuif

  • Ch - Centre Hospitalier Intercommunal

    Villeneuve-Saint-Georges, 94190

Other trials in France

About this study

Official title: Multicenter Randomized Phase II Study Comparing the Effectiveness and Tolerance of Avelumab Versus Standard 2nd Line Treatment Chemotherapy in Patients With Colorectal Metastatic Cancer With Microsatellite Instability (MSI)

Immune chekpoints (ICI) are evaluated in many digestive cancers. Certain types of cancer appear to be rather refractory to ICI such as colorectal cancers (CRC). However, the MSI CRC representing approximately 15% of the CRCs exhibits a high mutational load which generates many potentially immunogenic neoantigens. In addition, strong expression of PD-L1 was found in the MSI CRCs relative to the CRC (MSS) stages. Localized MSI CRCs have a better prognosis than MSS CRCs, probably due to immunogenic neoantigens associated with a CD8 + T-specific immune response. On the oher hand, in metastatic CRC (mCRC) things are different because i) the MSI frequency is only 4 to 7% and ii) the good prognosis conferred by the MSI status is controversial.

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.

Read more

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.

Being tested
FOLFOX regimen, FOLFIRI Protocol, Avelumab, Panitumumab, Cetuximab
Keywords
immunotherapy, second line
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOX regimenDrug

    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 ProtocolDrug

    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

  • AvelumabDrug

    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

  • PanitumumabDrug

    Administered at 6 mg/Kg

  • CetuximabDrug

    Administered at 500 mg/m²

  • BevacizumabDrug

    Administered at 5 mg/Kg

  • AfliberceptDrug

    Administered at 4 mg/Kg

Study groups in NCT03186326
Study groupRoleWhat they receive
Arm A Chemotherapy (standard treatment)Active comparatorFOLFOX or FOLFIRI +/- targeted therapy
Receives: Drug: FOLFOX regimen; Drug: FOLFIRI Protocol; Drug: Panitumumab; Drug: Cetuximab; Drug: Bevacizumab; Drug: Aflibercept
Arm B - Immunotherapy (experimental arm)ExperimentalAvelumab
Receives: Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS) according to the investigator

    Progression is defined as RECIST v1.1 criteria. Death is also considered as an event

    Measured: up to 12 months

Secondary outcomes (1)

  1. Overall Survival

    Defined as death due to all causes

    Measured: up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2017
  2. Study start24 Apr 2018
  3. Primary completion31 May 2022
  4. Study completion1 Mar 2025

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03186326
Sponsor's protocol ID
PRODIGE 54 - FFCD 1603
Acronym
SAMCO
Status last verified
Jun 2025
First submitted
17 May 2017
Last updated
29 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 33359404

  • 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.

    PubMed 40531517

  • 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.

    PubMed 37535388

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing FOLFOX regimen, FOLFIRI Protocol and Avelumab in people with Metastatic Colorectal Cancer and MSI, run by Federation Francophone de Cancerologie Digestive at 120 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: finished, as of the sponsor's last update on 29 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 120 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) according to the investigator (time frame: up to 12 months). 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 NCT03186326, which also lists 3 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 29 Jun 2025.

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