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

Sponsor
Federation Francophone de Cancerologie Digestive
Study ID
NCT03186326
Phase
PHASE2
Status
Completed

Conditions

  • MSI
  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • FOLFOX regimen — DRUG
    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 — DRUG
    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 — DRUG
    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 — DRUG
    Administered at 6 mg/Kg
  • Cetuximab — DRUG
    Administered at 500 mg/m²
  • Bevacizumab — DRUG
    Administered at 5 mg/Kg
  • Aflibercept — DRUG
    Administered at 4 mg/Kg

Study Details

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.

Key Dates

Start date
Apr 24, 2018
Status verified
Jun 2025
Primary completion
May 31, 2022
Completion
Mar 1, 2025

Study Design

Enrollment
132 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm A Chemotherapy (standard treatment)
    FOLFOX or FOLFIRI +/- targeted therapy
  • Experimental: Arm B - Immunotherapy (experimental arm)
    Avelumab

Primary Outcome Measure

Progression-free survival (PFS) according to the investigator [ Time Frame: up to 12 months ]

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