Trial Title:
Combination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas
NCT ID:
NCT06346197
Condition:
Gastric Cancer
MSI-H
Metastatic Cancer
Advanced Cancer
Conditions: Official terms:
Adenocarcinoma
Nivolumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Balstilimab
Description:
Balstilimab: 240mg, IV, Q2W, until disease progression, unacceptable toxicity, patient or
investigator decision or up to 2 years.
Arm group label:
Experimental arm
Intervention type:
Drug
Intervention name:
Botensilimab
Description:
Botensilimab: 75mg, IV for up to 4 doses, Q6W until disease progression, unacceptable
toxicity, patient or investigator decision or up to 2 years.
Arm group label:
Experimental arm
Intervention type:
Drug
Intervention name:
Folfox Protocol
Description:
oxaliplatin 85 mg/m2 , leucovorin 400 mg/m2 , and fluorouracil 400 mg/m2 administered IV
on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over
24 hours daily or per local standard on Days 1 and 2 of each treatment cycle, every 2
weeks.Treatment is recommended until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.
Arm group label:
Standard arm
Intervention type:
Drug
Intervention name:
XELOX
Description:
Oxaliplatin 130mg/m² IV on Day 1 of each treatment cycle + capecitabine 1000mg/m² orally
twice daily on Days 1 to 14 of each treatment cycle, every 3 weeks. Treatment is
recommended until disease progression, unacceptable toxicity, or up to 24 months in
patients without disease progression.
Arm group label:
Standard arm
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
240mg, IV, Q2. Treatment is recommended until disease progression, unacceptable toxicity,
or up to 24 months in patients without disease progression.
Arm group label:
Standard arm
Summary:
CIME is a multicenter, randomised, comparative, open-label phase III study aiming to
compare the survival of patients suffering from MSI-H/dMMR locally advanced or metastatic
oeasogastric adenocarcinoma treated by a bi-immunotherapy (experimental arm) versus
standard current treatment (FOLFOX/XELOX + nivolumab : standard arm).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Male or female patient ≥18 years of age at time of informed consent form signature.
- Patient with MSI-H/dMMR, HER2 negativeadvanced or metastatic gastric,
gastro-oesophageal junction or oesophageal adenocarcinoma whose tumours express
PD-L1 with a combined positive score (CPS) ≥ 5.
- Patient to be treated with a first line therapy for locally advanced/metastatic
disease.
- No prior treatment with chemotherapy for locally advanced/metastatic disease.
o Note - adjuvant or neoadjuvant chemotherapy is allowed providing that 6 months
have relapsed between completion of adjuvant chemotherapy and recurrence.
- Measurable disease (outside any previous irradiated field within the past 6 months)
defined as at least one unidimensional lesion that can be accurately measured as ≥
10 mm with CT scan according to RECIST V1.1 (Appendix 01).
- Note: Lesions intended to be biopsied should not be defined as target lesions.
- Note: previously irradiated lesions can be selected as target lesion only if
recurrence/PD is documented after RT.
- Patient with PS ECOG 0 or 1 (Appendix 02).
- Adequate hematologic and end-organ function, defined by the following laboratory
test results:
Absolute neutrophil count ≥ 1.5 109/L (without growth factor support within 14 d)
Platelets ≥ 100 109/L (without transfusion for platelets within 7 d) Hemoglobin ≥ 9 g/dL
(without transfusion within 7 d) Creatinine clearance according to CKD-EPI ≥ 30
mL/min/1.73 m2 Serum total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert
disease for whom a total serum bilirubin ≤ 3 x ULN is acceptable) ASAT and ALAT ≤ 3 x ULN
(or up to 5 x ULN in case of liver metastasis or hepatic infiltration)
- Availability of a representative formalin-fixed paraffin-embedded (FFPE) sample of
the primary or metastatic tumor tissue (resection or biopsy) with an associated
pathology report must be available. This tumor sample must meet the following
quality/quantity control criteria: ≥30 % of tumor cells and a tumor surface area ≥
5mm2 or biopsiable disease (see next inclusion criteria).
- Tumor lesion visible by medical imaging and accessible to repeatable percutaneous or
endoscopic sampling that permits core needle biopsy without unacceptable risk of a
significant procedural complications, and suitable for retrieval of a minimum of 4
cores with a needle minimum diameter :16-gauge.
- Note 1: Fine needle aspirates, bone biopsies do not satisfy the requirement for
tumor tissue.
- Note 2: Tumor lesions used for biopsy should not be lesions used as RECIST 1.1
target lesions unless there are no other lesions suitable for biopsy. If a
RECIST target lesion is used for biopsy, the lesion must be ≥ 2 cm in longest
diameter.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at
the Screening Visit (within 72 hours of first dose of study drugs) and must agree to
use highly effective contraceptive measures starting with the Screening Visit
through
- 9 months after the end of the treatment with oxaliplatin
- 6 months after the end of the treatment with fluorouracil
- 5 months after the end of the treatment with nivolumab or botensilimab or
Balstilimab
- 6 months for capecitabine
- Highly effective contraception is defined in Appendix 03.
Note Non-childbearing potential is defined as:
1. ≥ 50 years of age and has not had menses for greater than 1 year.
2. Amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy and a
follicle-stimulating hormone value in the postmenopausal range upon pre-study
(screening) evaluation.
3. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.
- Male patients with a female partner(s) of childbearing potential must agree to
use highly effective contraceptive measures throughout the study starting with
the screening visit through 6 months after the end of the treatment with
oxaliplatine or 3 months after the last dose for other study treatments is
received. Males with pregnant partners must agree to use a condom; no
additional method of contraception is required for the pregnant partner.
- Patient should understand, sign, and date the written voluntary informed
consent form prior to any protocol-specific procedures performed and should be
able and willing to comply with study visits and procedures as per protocol.
- Patients must be covered by a medical insurance.
Exclusion Criteria:
- Oesogastric cancer eligible to treatment with curative intent
- Patients previously treated by anti-PD-1, anti-PD-L1, or anti-CTLA-4 or any other
immunotherapy
- Patients with surgery or radiotherapy within less than 4 weeks before C1D1
- Patients with persistent AE Grade >1 related to previous anti-cancer treatment,
except alopecia (all grades), laboratory value according to criteria I7.
- Patients with: hypokalemia, hypomagnesemia, hypocalcemia less than normal
- Patients with known prolongation QT/QTc interval i.e. QT/QTc interval longer than
450 msec for men and longer than 470 msec for women according to the inclusion ECG.
- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.
Note: Asymptomatic patients with treated CNS lesions are eligible, provided that all of
the following criteria are met:
- Measurable disease, per RECIST v1.1, must be present outside the CNS.
- The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
- Metastases are limited to the cerebellum or the supratentorial region (i.e., no
metastases to the midbrain, pons, medulla, or spinal cord).
- There is no evidence of interim progression between completion of CNS-directed
therapy and initiation of study treatment.
- The patient has not undergone stereotactic radiotherapy within 7 days prior to
initiation of study treatment, whole-brain radiotherapy within 14 days prior to
initiation of study treatment, neurosurgical resection within 21 days prior to
initiation of study treatment.
- The patient has no ongoing requirement for corticosteroids as therapy for CNS
disease. Anticonvulsant therapy at a stable dose is permitted. A minimal wash-out
period of 10days for corticosteroids is required.
- Patients with other malignancy unless this malignancy is not expected to
interfere with the evaluation of study endpoints (basal or squamous cell
carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate
cancer), or with no evidence of disease for ≥ 2 years.
- Known allergy or hypersensitivity to any of the study drugs or any of the study
drug excipients.
- of ILD or non-infectious pneumonitis requiring glucocorticoids.
- History of allogeneic organ transplant.
- Psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study.
- Patient with peripheral sensory neuropathy with functional impairment.
- Patients with clinically significant active heart disease or myocardial
infarction within 6 months, history of uncontrolled or symptomatic cardiac
disease.
- Patient with recent (within 7d before C1D1) or concomitant treatment with
brivudine.
- Patient with complete absence of dihydropyrimidine dehydrogenase (DPD) activity
(blood uracil level ≥ 150 ng/mL) or partial deficit in DPD (i.e. blood uracil
level between ≥ 16 ng/ml and < 150 ng/mL)
- Patients with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or another
immunosuppressive medication within 30 days of the first dose of study
treatment. Inhaled or topical steroids, and adrenal replacement steroid doses
(≤ 10 mg daily prednisone equivalent) are permitted in the absence of active
autoimmune disease.
- Patient with Live vaccines injection within 4 weeks before C1D1. Examples of
live vaccines include, but are not limited to, the following: measles, mumps,
rubella, chicken pox, yellow fever and BCG. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however
intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines,
and are not allowed.
- Active autoimmune disease or history of autoimmune disease that required
systemic treatment within 2 years of the start of study treatment (i.e., with
use of disease-modifying agents or immunosuppressive drugs).
- History or current evidence of any condition, co-morbidity, therapy, any active
infections, or laboratory abnormality that might confound the results of the
study, interfere with the patient's participation for the full duration of the
study, or is not in the best interest of the patient to participate, in the
opinion of the treating Investigator.
- Patients with documented:
- Active hepatitis B (chronic or acute; defined as having a positive hepatitis B
surface antigen [HBsAg] test at screening) unless their HBV is stably controlled on
nucleoside analogs (eg entecavir or tenofovir) which will be continued for the
duration of the study. Note: Patients with past hepatitis B virus (HBV) infection or
resolved HBV infection (defined as the presence of hepatitis B core antibody
[anti-HBc] and absence of HBsAg) are eligible. HBV DNA test must be performed in
these patients prior to C1D1.
- Active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are
eligible only if PCR is negative for HCV RNA, or
- HIV infection
- Prior organ or bone marrow transplant.
- Pregnant or lactating women.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Country:
France
Contact:
Last name:
Clélia COUTZAC, MD
Email:
clelia.coutzac@lyon.unicancer.fr
Start date:
October 15, 2024
Completion date:
May 15, 2028
Lead sponsor:
Agency:
Centre Leon Berard
Agency class:
Other
Collaborator:
Agency:
Agenus Inc.
Agency class:
Industry
Source:
Centre Leon Berard
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06346197
