Gut microbiome intervention with EXL01 in combination with nivolumab and FOLFOX as first-line treatment for patients with PD-L1 CPS =5 metastatic gastric cancer: A randomized GERCOR phase II study (BIG)
- Conditions
- metastatic gastric adenocarcinomaMedDRA version: 21.1Level: LLTClassification code: 10071114Term: Metastatic gastric adenocarcinoma Class: 10029104Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- CTIS2023-506753-38-00
- Lead Sponsor
- Gercor
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 120
Patients must have dated and signed an approved written informed consent form. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care, Availability of a representative tumor tissue specimen for exploratory translational research; tumor tissue samples, either formalin-fixed paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections (minimum of 20 positively charged slides) from primary or metastatic site must be submitted to the central laboratory,, Registration in a national health care system (PUMa-Protection Universelle Maladie included., Age = 18 years, Women must not be pregnant, breastfeeding, or expecting to conceive during the study, Reproductive status: a.Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug, b.WOCBP must agree to use an adequate method of contraception or birth control for the duration of study treatment and 5 months (nivolumab), 4 months (oxaliplatin), 6 months (5-FU) or at least 1 month (EXL01) of the patient’s last dose of the study drug, c.Males who are fertile and sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and 6 months (nivolumab, oxaliplatin, or 5-FU) or at least 1 month (EXL01) after the last dose of study treatment. In addition, males must be willing to refrain from sperm donation during this time,, Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study, Inoperable, advanced, or metastatic gastric cancer or gastroesophageal junction or distal esophageal carcinoma and histologically confirmed predominant adenocarcinoma,, Expression of PD-L1 with a combined positive score (PD-L1 CPS) =5, No prior systemic cancer treatment given as primary therapy for advanced nonresectable or metastatic disease, NB: if patient received neoadjuvant/adjuvant therapy, this therapy should be completed at least 6 months prior to the diagnosis of metastatic or recurrent disease is made. Palliative radiotherapy is allowed and must be completed 2 weeks prior to randomization, At least one measurable lesion as assessed by computed tomography (CT)-scan or magnetic resonance imaging (MRI) according to RECIST v 1.1 and feasibility of repeated radiological assessments; radiographic tumor assessment should be performed within 28 days prior to randomization, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization of study treatment:, Baseline-corrected QT interval = 450 msec for males and = 470 msec for females,
Known HER-2 positive status, Major surgery within 28 days (4 weeks) prior to first dose of study treatment,, Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, radiotherapy, immunotherapy),, GI obstruction, poor oral intake, or difficulty in taking oral medication or difficulties in swallowing; nasogastric tubes are not permitted,, Known GI malabsorption,, Is currently participating in or has participated in a study with an investigational compound within 28 days prior to the first dose of study treatment, Prior allogeneic bone marrow transplantation or prior solid organ transplantation, Fecal microbiota transplant within 3 months prior to screening, Note: Patients must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention., Probiotics or prebiotic supplements should be avoided during the study,, Excessive alcohol intake: moderate consumption, defined as no more than 1 drink per day for women and no more than 2 drinks per day for men, is permitted,, Known allergy and/or hypersensitivity to any component or excipients of study treatments (nivolumab, EXL01), any other live pro-biotherapeutic product, and/or to soybean or soy-containing products,, Active brain metastases or known history of leptomeningeal carcinomatosis, Known history or newly diagnosed GI parasitic infection within 3 months prior to screening, NB: Patients must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention,, Active or chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and/or human immunodeficiency virus infection (HIV 1/2 antibodies). Participants are eligible if they: -Have controlled HCV load defined as undetectable hepatitis C RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C therapy, -Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis, -Are HBV surface antigen (HBsAg)- and anti- Hepatitis B core antibody (HBc)+ (i.e., those who have cleared HBV after infection), -Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions below: •HBV DNA viral load <100 IU/mL, •Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT <3 × ULN, which are not attributable to HBV infection, •Start or maintain antiviral treatment if clinically indicated as per the investigator, Any (attenuated) live vaccine use within 28 days (4 weeks) prior to randomization, while in the study; live vaccines include, but are not limited to, the following: yellow fever, varicella, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza, Ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine, Known dihydropyrimidine dehydrogenase deficiency (partial or complete),, Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of the patient’s safety or study results,, Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness, Patient under a legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapable of giving his/her consent., Ascites, which cannot be controlled with appropriate intervent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method