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Solid cancers are frequently treated with chemotherapies that target the DNA of cancer cells. It has recently come to light that bacteria are also the target of chemotherapies used in oncology. The results of current studies demonstrate the close link between the composition of the microbiota, the immune system, toxicity and the efficacy or otherwise of anti-cancer treatments.
In this context, the study will measure the influence of treatment with anticancer molecules known to activate the bacterial SOS response on the emergence of antibiotic-resistant commensal bacteria in the gut microbiota of cancer patients. Furthermore, this study will investigate the existence of a close link between changes in the intestinal microbiota determined by the induction or non-induction of the SOS response, bacterial translocation, the integrity of the intestinal barrier and the antitumor immune response.
The RAMA trial plans to collect stool and blood samples from two different cohorts of patients:
Patients' stools will be collected within 7 days of their first chemotherapy treatment and within 7 days of the 3rd chemotherapy cycle. Two blood samples will be taken at the same time as the stool samples.
The results obtained from this prospective clinical research will then be investigated in two experimental laboratory models.
The aim is to demonstrate that cytotoxic anticancer drugs promote the emergence of antibiotic-resistant commensal bacteria, by means of this large-scale study comprising a clinical component, which is the subject of the research presented in this protocol, combined with laboratory research components.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All cohorts | Experimental | For each cohort :
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mandatory biological samples (blood and sell) | Other | At cycle 1 and Cycle 3 :
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Determine whether the digestive microbiota of patients exposed to SOS-inducing cytotoxic cancer drugs favors the emergence of antibiotic-resistant commensal bacteria compared to patients exposed to other non-SOS-inducing cytotoxic cancer drugs. | The primary endpoint is the emergence of antibiotic-resistant Enterobacteriaceae, defined as the presence of Enterobacteriaceae resistant to 3rd-generation cephalosporins and/or fluoroquinolones on the sample taken within 7 days of administration of the 3rd cycle of chemotherapy, compared with the pretreatment initiation sample taken within 7 days of administration of the first cycle of chemotherapy. | up to 3 months |
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Inclusion Criteria:
Men and women over 18
Chemotherapy-naive patients.
Patients due to start chemotherapy/radio chemotherapy who meet the criteria of the cohorts listed below :
OMS ≤ 2
Affiliation with a French social security scheme or beneficiary of such a scheme.
Signed informed consent indicating that the patient has understood the purpose and procedures of the study and agrees to participate in the study and to abide by the study requirements and restrictions
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sylvain LADOIRE, Professor | Contact | 03 80 73 75 00 | +33 | SLadoire@cgfl.fr |
| Anne-Laure REROLE, Projet manager | Contact | 03 45 34 88 46 | +33 | arerole@cgfl.fr |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| D016889 | Endometrial Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D016201 | Receptors, Lymphocyte Homing |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D015815 | Cell Adhesion Molecules |
| D008562 | Membrane Glycoproteins |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008565 | Membrane Proteins |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D000954 | Antigens, Surface |
| D000941 | Antigens |
| D001685 | Biological Factors |
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