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

  • STATUS
    Recruiting
  • End date
    Mar 31, 2025
  • participants needed
    132
  • sponsor
    Federation Francophone de Cancerologie Digestive
Updated on 29 December 2019
Investigator
Jérémie BEZ
Primary Contact
Hopital Drome Nord (9.9 mi away) Contact
+169 other location
carcinoma
metastasis
oxaliplatin
capecitabine
avelumab
panitumumab
liver metastasis
irinotecan
bevacizumab
primary tumor
folfox regimen
cetuximab
adenocarcinoma
aflibercept
adjuvant chemotherapy
folfiri regimen
colorectal adenocarcinoma
microsatellite instability high

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.

Details
Treatment Panitumumab, Cetuximab, bevacizumab, Aflibercept, Avelumab, FOLFOX regimen, FOLFIRI Protocol
Clinical Study IdentifierNCT03186326
SponsorFederation Francophone de Cancerologie Digestive
Last Modified on29 December 2019

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Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Metastatic Colorectal Cancer or Microsatellite Instability?
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

Exclusion Criteria

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)
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
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