NCT03186326|CompletedPhase 2DMC

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

SAMCO

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)

Federation Francophone de Cancerologie Digestive ClinicalTrials.gov

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1 other identifier

PRODIGE 54 - FFCD 1603

Study Type

interventional

Target

132

Locations

1 country

Sites

120

Timeline

RegisteredJun 2017

StartedApr 2018

CompletionMar 2025

Brief 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. 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. 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

132

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Apr 2018

Longer than P75 for phase_2

Geographic Reach

1 country

120 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

6.9 years study duration

First Submitted

Initial submission to the registry

May 17, 2017

Completed

28 days until next milestone

First Posted

Study publicly available on registry

June 14, 2017

Completed

10 months until next milestone

Study Start

First participant enrolled

April 24, 2018

Completed

4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2022

Completed

2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2025

Completed

Last Updated

June 29, 2025

Status Verified

June 1, 2025

Enrollment Period

4.1 years

First QC Date

May 17, 2017

Last Update Submit

June 27, 2025

Conditions

Metastatic Colorectal Cancer MSI

Keywords

immunotherapysecond line

Outcome Measures

Primary Outcomes (1)

Progression-free survival (PFS) according to the investigator
Progression is defined as RECIST v1.1 criteria. Death is also considered as an event
up to 12 months

Secondary Outcomes (1)

Overall Survival
up to 60 months

Study Arms (2)

Arm A Chemotherapy (standard treatment)

ACTIVE COMPARATOR

FOLFOX or FOLFIRI +/- targeted therapy

Drug: FOLFOX regimenDrug: FOLFIRI ProtocolDrug: PanitumumabDrug: CetuximabDrug: BevacizumabDrug: Aflibercept

Arm B - Immunotherapy (experimental arm)

EXPERIMENTAL

Avelumab

Drug: Avelumab

Interventions

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