Standard Chemotherapy vs Immunotherapie in 2nd Line Treatment of MSI Colorectal Mestastatic Cancer (SAMCO)
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|ClinicalTrials.gov Identifier: NCT03186326|
Recruitment Status : Active, not recruiting
First Posted : June 14, 2017
Last Update Posted : August 19, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Cancer MSI||Drug: FOLFOX regimen Drug: FOLFIRI Protocol Drug: Avelumab Drug: Panitumumab Drug: Cetuximab Drug: Bevacizumab Drug: Aflibercept||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||132 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||April 24, 2018|
|Actual Primary Completion Date :||May 31, 2022|
|Estimated Study Completion Date :||May 31, 2023|
Active Comparator: Arm A Chemotherapy (standard treatment)
FOLFOX or FOLFIRI +/- targeted therapy
Drug: 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
Drug: 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
Administered at 6 mg/Kg
Administered at 500 mg/m²
Administered at 5 mg/Kg
Administered at 4 mg/Kg
Experimental: Arm B - Immunotherapy (experimental arm)
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.
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
- Progression-free survival (PFS) according to the investigator [ Time Frame: up to 12 months ]Progression is defined as RECIST v1.1 criteria. Death is also considered as an event
- Overall Survival [ Time Frame: up to 60 months ]Defined as death due to all causes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03186326
|Principal Investigator:||Julien Taieb, Pr||HOPITAL EUROPEEN G. POMPIDOU|