Informations générales (source: ClinicalTrials.gov)
Peri-operative Association of Immunotherapy (Pre-operative Association of Nivolumab and Ipilimumab, Post-operative Nivolumab Alone) in Localized Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR) Oeso-gastric Adenocarcinoma: An Open-label GERCOR Phase II Study (NEONIPIGA)
Interventional
Phase 2
GERCOR - Multidisciplinary Oncology Cooperative Group (Voir sur ClinicalTrials)
octobre 2019
juin 2024
29 juin 2024
This is a non-randomized study, open label phase II study. The purpose of this study is
to evaluate the complete pathologic response rate (cPRR) with neoadjuvant nivolumab and
ipilimumab combination in patients with MSI and/or dMMR localized oeso-gastric cancer.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Saint Antoine | Thierry ANDRE, MD | Contact (sur clinicalTrials) | |||
| EFS IDF SITE HOP EUROPEEN G POMPIDOU | Aziz ZANNAN, MD | Contact (sur clinicalTrials) | |||
| IFSI DE L'HÔPITAL SAINT LOUIS | Thomas APARICIO, MD | Contact (sur clinicalTrials) | |||
| INSTITUT MUTUALISTE MONTSOURIS | Christophe LOUVET, MD | Contact (sur clinicalTrials) | |||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CHRU Jean Minjoz - Besançon - France | Marine JARY, MD | Contact (sur clinicalTrials) | |||
| CHU Poitiers - Poitiers - France | David TOUGERON, MD | Contact (sur clinicalTrials) | |||
| CHU Toulouse - Toulouse - France | Rosine GUIMBAUD, MD | Contact (sur clinicalTrials) | |||
| Hôpital Privé Jean Mermoz - Lyon - France | Léa CLAVEL, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Léon Bérard - 69373 - Lyon - France | Clélia COUTZAC, MD | Contact (sur clinicalTrials) | |||
| CHRU Lille - Lille - France | Guillaume PIESSEN, MD | Contact (sur clinicalTrials) | |||
| CHU Nantes - Nantes - France | Solange PECOUT, MD | Contact (sur clinicalTrials) | |||
| CHU Pontchaillou Rennes - 35033 - Rennes - France | Astrid LIEVRE, MD | Contact (sur clinicalTrials) | |||
| Hôpital Henri Mondor - Créteil - France | Christophe TOURNIGAND, MD | Contact (sur clinicalTrials) | |||
| ICM Val d'Aurelle - Montpellier - France | Antoine ADENIS, MD | Contact (sur clinicalTrials) | |||
| Institut Hospitalier Franco-Britannique - Levallois-Perret - France | Benoist CHIBAUDEL, Md | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Signed and dated informed consent,
2. Age ≥18 years to ≤75 years of age,
3. Histologically proven non-metastatic gastric adenocarcinoma or of the oeso-gastric
junction T2 to T4, Nx, M0 after thoraco-abdominopelvic computed tomography (CT) and
echo-endoscopy,
4. Subjects must be willing and able to comply with scheduled visits, treatment
schedule, laboratory tests, tumor biopsies, and other requirements of the study,
5. dMMR (protein expression by immunohistochemistry [ICH] and/or MSI by polymerase
chain reaction [PCR]), MMR and/or MSI tumors should be assessed per local
guidelines: ICH with two (anti-MLH1 and anti-MSH2 or anti-MSH6, and antiPMS2) or
four antibodies (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) and/or PCR (with
PROMEGA: BAT- 25, BAT-26, NR-21, NR-24, and NR-27) by the investigators prior to
screening, Extinct MLH1 (+/- PMS2), MSH2 (+/- MSH6), MSH6, or PMS2 alone protein
expression by IHC (dMMR), and/or tumor with ≥ 2 instable MSI-H markers on PCR:
BAT25, BAT26, NR21, NR24, and NR27 (pentaplex panel is recommended),
6. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1, for
patients over 70 years ECOG PS of 0;
7. Hematological status: absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥100 x
109/L; hemoglobin ≥9 g/dL,
8. Adequate renal function: serum creatinine level <120 µM, clearance > 50ml/min
(Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault),
9. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline
phosphatase <5 x ULN, alanine aminotransferase (ALT), and aspartate aminotransferase
(AST) ≤3.0 x ULN,
10. No prior therapy for localized oeso-gastric cancer,
11. Radiological tumor assessment within 21 days before the start of treatment according
to RECIST version 1.1 by Chest Abdomen and Pelvis CT,
12. For female patients of childbearing potential, negative pregnancy test within 7 days
before starting the study drug,
13. Men and women are required to use adequate birth control during the study (when
applicable), Female participants of childbearing potential and male participants
with partners of childbearing potential must agree to use a highly effective method
of birth control (i.e., pregnancy rate of less than 1% per year) during the period
of treatment and during 5 and 7 months, woman and men, respectively, from the last
treatment administration. Men must refrain from donating sperm during this same
period, Contraceptive methods that result in a low failure rate when used
consistently and correctly include methods such as combined hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, transdermal),
progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, implantable), some intrauterine devices, intrauterine hormone-
releasing stem, true sexual abstinence (when this is in line with the preferred and
usual lifestyle of the participant), bilateral tubal occlusion, or a female partner
who is not of childbearing potential or a male partner who has had a vasectomy.
Women and female partners using hormonal contraceptive must also use a barrier
method i.e. condom or occlusive cap (diaphragm or cervical/vault caps), A woman is
considered to be of childbearing potential if she is postmenarcheal, has not reached
a postmenopausal state (>12 continuous months of amenorrhea with no identified cause
other than menopause), and has not undergone surgical sterilization (removal of
ovaries and/or uterus),
14. Subject willing to comply to provide primary tumor tissue (archival or fresh biopsy
specimen), including possible pre-treatment biopsy for PD-L1 expression analysis and
other biomarker correlative studies
15. Registration in a National Health Care System (PUMa - Protection Universelle Maladie
included)
1. Signed and dated informed consent,
2. Age ≥18 years to ≤75 years of age,
3. Histologically proven non-metastatic gastric adenocarcinoma or of the oeso-gastric
junction T2 to T4, Nx, M0 after thoraco-abdominopelvic computed tomography (CT) and
echo-endoscopy,
4. Subjects must be willing and able to comply with scheduled visits, treatment
schedule, laboratory tests, tumor biopsies, and other requirements of the study,
5. dMMR (protein expression by immunohistochemistry [ICH] and/or MSI by polymerase
chain reaction [PCR]), MMR and/or MSI tumors should be assessed per local
guidelines: ICH with two (anti-MLH1 and anti-MSH2 or anti-MSH6, and antiPMS2) or
four antibodies (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) and/or PCR (with
PROMEGA: BAT- 25, BAT-26, NR-21, NR-24, and NR-27) by the investigators prior to
screening, Extinct MLH1 (+/- PMS2), MSH2 (+/- MSH6), MSH6, or PMS2 alone protein
expression by IHC (dMMR), and/or tumor with ≥ 2 instable MSI-H markers on PCR:
BAT25, BAT26, NR21, NR24, and NR27 (pentaplex panel is recommended),
6. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1, for
patients over 70 years ECOG PS of 0;
7. Hematological status: absolute neutrophil count (ANC) ≥1.5 x 109/L; platelets ≥100 x
109/L; hemoglobin ≥9 g/dL,
8. Adequate renal function: serum creatinine level <120 µM, clearance > 50ml/min
(Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault),
9. Adequate liver function: serum bilirubin ≤1.5 x upper normal limit (ULN), alkaline
phosphatase <5 x ULN, alanine aminotransferase (ALT), and aspartate aminotransferase
(AST) ≤3.0 x ULN,
10. No prior therapy for localized oeso-gastric cancer,
11. Radiological tumor assessment within 21 days before the start of treatment according
to RECIST version 1.1 by Chest Abdomen and Pelvis CT,
12. For female patients of childbearing potential, negative pregnancy test within 7 days
before starting the study drug,
13. Men and women are required to use adequate birth control during the study (when
applicable), Female participants of childbearing potential and male participants
with partners of childbearing potential must agree to use a highly effective method
of birth control (i.e., pregnancy rate of less than 1% per year) during the period
of treatment and during 5 and 7 months, woman and men, respectively, from the last
treatment administration. Men must refrain from donating sperm during this same
period, Contraceptive methods that result in a low failure rate when used
consistently and correctly include methods such as combined hormonal contraception
associated with inhibition of ovulation (oral, intravaginal, transdermal),
progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, implantable), some intrauterine devices, intrauterine hormone-
releasing stem, true sexual abstinence (when this is in line with the preferred and
usual lifestyle of the participant), bilateral tubal occlusion, or a female partner
who is not of childbearing potential or a male partner who has had a vasectomy.
Women and female partners using hormonal contraceptive must also use a barrier
method i.e. condom or occlusive cap (diaphragm or cervical/vault caps), A woman is
considered to be of childbearing potential if she is postmenarcheal, has not reached
a postmenopausal state (>12 continuous months of amenorrhea with no identified cause
other than menopause), and has not undergone surgical sterilization (removal of
ovaries and/or uterus),
14. Subject willing to comply to provide primary tumor tissue (archival or fresh biopsy
specimen), including possible pre-treatment biopsy for PD-L1 expression analysis and
other biomarker correlative studies
15. Registration in a National Health Care System (PUMa - Protection Universelle Maladie
included)
Non-eligible to clinical trial if one of following parameter is reported:
1. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted
therapy, immunotherapy),
2. Treatment with any investigational medicinal product within 28 days prior to study
entry,
3. Major surgical procedure within 4 weeks prior to initiation of study treatment,
4. Other serious and uncontrolled non-malignant disease (including active infection),
5. Other concomitant or previous malignancy, except: i/ adequately treated in-situ
carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin,
iii/ cancer in complete remission for >5 years,
6. Metastases (M stage disease) whatever the location,
7. Pregnant or breastfeeding women,
8. Human immunodeficiency virus (HIV),
9. Active hepatitis B virus (HBV, defined as having a positive hepatitis B surface
antigen [HBsAg] test prior to inclusion) or hepatitis C virus (HCV). Note: Patients
with past HBV infection or resolved HBV infection (defined as having a negative
HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are
eligible. Note: Patients positive for HCV antibody are eligible only if PCR testing
is negative for HCV RNA
10. Patient on tutelage or guardianship or under the protection of justice.
11. Impossibility of submitting to the medical follow-up of the study for geographical,
social or psychiatric reasons.
Non-eligible to immunotherapy:
1. History of autoimmune disease including, but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis, Note: History of
autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone
may be eligible. Note: Controlled Type 1 diabetes mellitus on a stable insulin
regimen may be eligible.
2. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest imaging,
3. Administration of a live, attenuated vaccine within 4 weeks prior to start of
treatment or anticipation that such a live attenuated vaccine will be required
during the remainder of the study,
4. Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or antiPD-L1 therapeutic
antibody or pathway-targeting agents,
5. Prior allogeneic bone marrow transplantation or prior solid organ transplantation,
6. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including, but not limited to prednisone, dexamethasone,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) within 2 weeks prior to start of adjuvant treatment, or requirement
for systemic immunosuppressive medications during the remainder of the study.
Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone
equivalents are permitted in the absence of active autoimmune disease.
Note: Patients who have received acute, low-dose, systemic immunosuppressant medications
(e.g., a one-time dose of dexamethasone for nausea) may be enrolled into the study after
approval of the Medical Contact. Subjects are permitted the use of topical, ocular,
intra- articular, intranasal, and inhalational corticosteroids (with minimal systemic
absorption).
Adrenal replacement steroid doses including doses >10 mg daily prednisone is permitted. A
brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g. contrast dye
allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type
hypersensitivity reaction caused by a contact allergen) is permitted