Combination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas
- Conditions
- Gastric CancerAdvanced CancerMSI-HMetastatic Cancer
- Registration Number
- NCT06346197
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not yet recruiting
- Sex
- All
- Target Recruitment
- 124
Inclusion Criteria:<br><br> - Male or female patient =18 years of age at time of informed consent form signature.<br><br> - Patient with MSI-H/dMMR, HER2 negativeadvanced or metastatic gastric,<br> gastro-oesophageal junction or oesophageal adenocarcinoma whose tumours express<br> PD-L1 with a combined positive score (CPS) = 5.<br><br> - Patient to be treated with a first line therapy for locally advanced/metastatic<br> disease.<br><br> - No prior treatment with chemotherapy for locally advanced/metastatic disease.<br><br> o Note - adjuvant or neoadjuvant chemotherapy is allowed providing that 6 months<br> have relapsed between completion of adjuvant chemotherapy and recurrence.<br><br> - Measurable disease (outside any previous irradiated field within the past 6 months)<br> defined as at least one unidimensional lesion that can be accurately measured as =<br> 10 mm with CT scan according to RECIST V1.1 (Appendix 01).<br><br> - Note: Lesions intended to be biopsied should not be defined as target lesions.<br><br> - Note: previously irradiated lesions can be selected as target lesion only if<br> recurrence/PD is documented after RT.<br><br> - Patient with PS ECOG 0 or 1 (Appendix 02).<br><br> - Adequate hematologic and end-organ function, defined by the following laboratory<br> test results:<br><br>Absolute neutrophil count = 1.5 109/L (without growth factor support within 14 d)<br>Platelets = 100 109/L (without transfusion for platelets within 7 d) Hemoglobin = 9 g/dL<br>(without transfusion within 7 d) Creatinine clearance according to CKD-EPI = 30<br>mL/min/1.73 m2 Serum total bilirubin = 1.5 x ULN (except for patients with Gilbert<br>disease for whom a total serum bilirubin = 3 x ULN is acceptable) ASAT and ALAT = 3 x ULN<br>(or up to 5 x ULN in case of liver metastasis or hepatic infiltration)<br><br> - Availability of a representative formalin-fixed paraffin-embedded (FFPE) sample of<br> the primary or metastatic tumor tissue (resection or biopsy) with an associated<br> pathology report must be available. This tumor sample must meet the following<br> quality/quantity control criteria: =30 % of tumor cells and a tumor surface area =<br> 5mm2 or biopsiable disease (see next inclusion criteria).<br><br> - Tumor lesion visible by medical imaging and accessible to repeatable percutaneous or<br> endoscopic sampling that permits core needle biopsy without unacceptable risk of a<br> significant procedural complications, and suitable for retrieval of a minimum of 4<br> cores with a needle minimum diameter :16-gauge.<br><br> - Note 1: Fine needle aspirates, bone biopsies do not satisfy the requirement for<br> tumor tissue.<br><br> - Note 2: Tumor lesions used for biopsy should not be lesions used as RECIST 1.1<br> target lesions unless there are no other lesions suitable for biopsy. If a<br> RECIST target lesion is used for biopsy, the lesion must be = 2 cm in longest<br> diameter.<br><br> - Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at<br> the Screening Visit (within 72 hours of first dose of study drugs) and must agree to<br> use highly effective contraceptive measures starting with the Screening Visit<br> through<br><br> - 9 months after the end of the treatment with oxaliplatin<br><br> - 6 months after the end of the treatment with fluorouracil<br><br> - 5 months after the end of the treatment with nivolumab or botensilimab or<br> Balstilimab<br><br> - 6 months for capecitabine<br><br> - Highly effective contraception is defined in Appendix 03.<br><br>Note Non-childbearing potential is defined as:<br><br> 1. = 50 years of age and has not had menses for greater than 1 year.<br><br> 2. Amenorrheic for = 2 years without a hysterectomy and bilateral oophorectomy and a<br> follicle-stimulating hormone value in the postmenopausal range upon pre-study<br> (screening) evaluation.<br><br> 3. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.<br><br> - Male patients with a female partner(s) of childbearing potential must agree to<br> use highly effective contraceptive measures throughout the study starting with<br> the screening visit through 6 months after the end of the treatment with<br> oxaliplatine or 3 months after the last dose for other study treatments is<br> received. Males with pregnant partners must agree to use a condom; no<br> additional method of contraception is required for the pregnant partner.<br><br> - Patient should understand, sign, and date the written voluntary informed<br> consent form prior to any protocol-specific procedures performed and should be<br> able and willing to comply with study visits and procedures as per protocol.<br><br> - Patients must be covered by a medical insurance.<br><br>Exclusion Criteria:<br><br> - Oesogastric cancer eligible to treatment with curative intent<br><br> - Patients previously treated by anti-PD-1, anti-PD-L1, or anti-CTLA-4 or any other<br> immunotherapy<br><br> - Patients with surgery or radiotherapy within less than 4 weeks before C1D1<br><br> - Patients with persistent AE Grade >1 related to previous anti-cancer treatment,<br> except alopecia (all grades), laboratory value according to criteria I7.<br><br> - Patients with: hypokalemia, hypomagnesemia, hypocalcemia less than normal<br><br> - Patients with known prolongation QT/QTc interval i.e. QT/QTc interval longer than<br> 450 msec for men and longer than 470 msec for women according to the inclusion ECG.<br><br> - Symptomatic, untreated, or actively progressing central nervous system (CNS)<br> metastases.<br><br>Note: Asymptomatic patients with treated CNS lesions are eligible, provided that all of<br>the following criteria are met:<br><br> - Measurable disease, per RECIST v1.1, must be present outside the CNS.<br><br> - The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.<br><br> - Metastases are limited to the cerebellum or the supratentorial region (i.e., no<br> metastases to the midbrain, pons, medulla, or spinal cord).<br><br> - There is no evidence of interim progression between completion of CNS-directed<br> therapy and initiation of study treatment.<br><br> - The patient has not undergone stereotactic radiotherapy within 7 days prior to<br> initiation of study treatment, whole-brain radiotherapy within 14 days prior to<br> initiation of study treatment, neurosurgical resection within 21 days prior to<br> initiation of study treatment.<br><br> - The patient has no ongoing requirement for corticosteroids as therapy for CNS<br> disease. Anticonvulsant therapy at a stable dose is permitted. A minimal wash-out<br> period of 10days for corticosteroids is required.<br><br> - Patients with other malignancy unless this malignancy is not expected to<br> interfere with the evaluation of study endpoints (basal or squamous cell<br> carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate<br> cancer), or with no evidence of disease for = 2 years.<br><br> - Known allergy or hypersensitivity to any of the study drugs or any of the study<br> drug excipients.<br><br> - of ILD or non-infectious pneumonitis requiring glucocorticoids.<br><br> - History of allogeneic organ transplant.<br><br> - Psychiatric or substance abuse disorders that would interfere with cooperation<br> with the requirements of the study.<br><br> - Patient with peripheral
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Survival of patients
- Secondary Outcome Measures
Name Time Method Progression free survival;Objective response rate;Duration of response;Adverse Event description as assessed by CTCAE V5.0;EORTC QLQ C30