Trial Title:
First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer
NCT ID:
NCT06253611
Condition:
Gastric Cancer
Conditions: Official terms:
Stomach Neoplasms
Leucovorin
Nivolumab
Oxaliplatin
Fluorouracil
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Nivolumab 240 mg IV; every 2 weeks
Arm group label:
Nivolumab Combined With FOLFOX and EXL01
Arm group label:
Nivolumab and FOLFOX
Other name:
Opdivo
Intervention type:
Drug
Intervention name:
FOLFOX regimen
Description:
Oxaliplatin 85 mg/m², leucovorin 400 mg/m², bolus of 5-FU 400 mg/m², continuous 5-FU
2400/m² in 46 hours; every 2 weeks
Arm group label:
Nivolumab Combined With FOLFOX and EXL01
Arm group label:
Nivolumab and FOLFOX
Other name:
Leucovorin, fluorouracil, and oxaliplatin
Intervention type:
Biological
Intervention name:
EXL01
Description:
Orally 1 capsule/day, starting on day 1 of each FOLFOX/nivolumab treatment.
Arm group label:
Nivolumab Combined With FOLFOX and EXL01
Summary:
This is a randomized non-comparative, multicenter phase II study in patients with PD-L1
PD-L1 combined positive score (CPS) ≥5 advanced gastric cancer to evaluate the efficacy
and safety of nivolumab and FOLFOX in combination with EXL01 as first-line treatment.
After signing the informed consent form, and upon confirmation of the patient's
eligibility, patients will be randomized in a 2:1 ratio to either the nivolumab and
FOLFOX plus EXL01 arm (experimental) or the nivolumab and FOLFOX arm (control). In both
arms, treatment will be given until PD, unacceptable toxicity or for a maximum of 24
months (52 cycles).
Detailed description:
The primary objective of the study is to assess the objective response rate (ORR) at 4
months (based on Response Evaluation Criteria in Solid Tumor [RECIST] criteria) of
patients with PD-L1 CPS ≥ 5 advanced gastric cancer treated by EXL01 plus nivolumab and
FOLFOX as first-line treatment.
With a randomization ratio of 2:1 it will be necessary to randomize 40 patients in the
control arm, 80 patients in the experimental arm and so a total of 120 evaluable patients
in the study. Randomization will be stratified by PD-L1 expression level, center, and
prior gastrectomy.
In the experimental arm, the primary analysis will be on modified intent-to-treat (mITT)
population. Confirmative analysis will be conducted firstly in the ITT population and
secondly, in the Per Protocol (PP). Analyses of safety will be conducted in safety
population.
The Kaplan-Meier method will be used to estimate time to event endpoints and described
using the median and event-free rates over time with CI.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
The patient is eligible to be included in the study only if all of the following criteria
apply:
1. 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.
2. Patients must be willing and able to comply with scheduled visits, treatment
schedule, laboratory tests and other requirements of the study,
Target Population
3. Inoperable, advanced, or metastatic gastric cancer or gastroesophageal junction or
distal esophageal carcinoma and histologically confirmed predominant adenocarcinoma,
4. Expression of PD-L1 with a combined positive score (PD-L1 CPS) ≥5, Note: information
must be available at the time of inclusion, the examination will be performed
locally in the center and secondarily confirmed centrally,
5. No prior systemic cancer treatment given as primary therapy for advanced
nonresectable or metastatic disease, Nota bene (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,
6. At least one measurable lesion as assessed by computed tomography (CT)-scan or
magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid
Tumors (RECIST) v 1.1 and feasibility of repeated radiological assessments;
radiographic tumor assessment should be performed within 28 days prior to
randomization,
7. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1,
8. Adequate hematologic and end-organ function, defined by the following laboratory
test results, obtained within 14 days prior to randomization of study treatment:
1. White blood cell ≥ 2000/μL;
2. Neutrophils ≥ 2000/μL;
3. Platelets ≥ 100.000/μL;
4. Hemoglobin ≥ 9.0 g/dL;
5. Serum albumin ≥ 30 g/L;
6. Serum creatinine level ≤ 150 μM and calculated creatinine clearance
(Cockcroft-Gault) > 50 mL/minute,
7. Total bilirubin ≤ 1.5 x upper normal limit (ULN);
8. Alanine aminotransferase (ALT) ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver metastases
are present);
9. Aspartame aminotransferase (AST) ≤ 3.0 x ULN (or ≤ 5.0 x ULN if liver
metastases are present);
10. Potassium ≥ 1.0 x lower limit of normal (LLN),
11. Magnesium ≥ 1.0 x LLN,
12. Calcium ≥ 1.0 x LLN,
9. Baseline-corrected QT interval ≤ 450 msec for males and ≤ 470 msec for females,
10. 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,
11. Registration in a national health care system (PUMa-Protection Universelle Maladie
included.
Age and reproductive status
12. Age ≥ 18 years,
13. Women must not be pregnant, breastfeeding, or expecting to conceive during the
study,
14. Reproductive status:
1. Women of childbearing potential (WOCBP) must have a negative serum pregnancy
test within 72 hours prior to the start of study drug,
2. WOCBP must agree to use an adequate method of contraception or birth control
for the duration of study treatment and 5 months (nivolumab), 9 months
(oxaliplatin), 6 months (5-FU) or at least 1 month (EXL01) of the patient's
last dose of the study drug,
3. 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,
Exclusion Criteria:
The patient is ineligible for the study if any of the following criteria apply:
Target Disease Exceptions
1. Known HER-2 positive status or unknown HER-2 status before inclusion,
2. Active brain metastases or known history of leptomeningeal carcinomatosis,
3. Ascites, which cannot be controlled with appropriate interventions,
Exclusion criteria related to medical history and concurrent disease
4. Prior malignancy active within the previous 3 years except for locally curable
cancers that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast,
5. Active, known, or suspected autoimmune disease; type I diabetes mellitus,
hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo,
psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected
to recur in the absence of an external trigger are permitted,
6. Interstitial lung disease that is symptomatic or may interfere with the detection or
management of suspected treatment-related pulmonary toxicity,
7. Prior treatment with an anti-PD(L)1, anti-LAG-3, or anti-CTLA-4 antibody, or any
other antibody or drug specifically targeting T-cell co-stimulation or immune
checkpoint pathways, including prior therapy with anti-tumor vaccines or other
immuno-stimulatory antitumor agents,
8. Condition requiring systemic treatment with either corticosteroids (>10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days (2
weeks) of randomization. Inhaled or topical steroids, and adrenal replacement
steroid doses >10 mg daily prednisone equivalent, are permitted prior to
randomization in the absence of active autoimmune disease,
9. Persistence of toxicity (The National Cancer Institute Common Terminology Criteria
for Adverse Event [NCI CTCAE] v 5.0) grade >1 related to prior anticancer
treatments,
10. Major surgery within 28 days (4 weeks) prior to first dose of study treatment,
11. Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted
therapy, radiotherapy, immunotherapy),
Exclusion criteria related to EXL01
12. GI obstruction, poor oral intake, or difficulty in taking oral medication or
difficulties in swallowing; nasogastric tubes are not permitted,
13. Known GI malabsorption,
14. 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, NB: Participants
who have entered the follow-up phase of an investigational study may participate so
long as it has been at least 3 months since the last dose of the previous
investigational agent,
15. Prior allogeneic bone marrow transplantation or prior solid organ transplantation,
16. 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.
17. Current probiotics administration, or planned probiotics administration during
treatment course is not allowed,
NB: The following therapies should be avoided during the study; however, they are
not prohibited if, in the assessment of the Investigator, they are required for
clinical management:
- Nonsteroidal anti-inflammatories,
- Antacids,
- Proton-pump inhibitors.
18. 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,
19. 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,
20. 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,
21. Active inflammatory intestinal disease (Crohn disease, Hemorrhagic recto-colitis,
coeliac disease) or any serious chronic intestinal disease with uncontrolled
diarrhea, or other inflammatory disease requiring anti-inflammatory medications
(according to exclusion criteria n°8),
Exclusion criteria related to chemotherapy
22. 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 polymerase
chain reaction 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,
23. 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,
24. Ongoing or concomitant use of the antiviral drug sorivudine or its chemically
related analogs, such as brivudine,
25. Dihydropyrimidine dehydrogenase deficiency (DPD; uracilemia dosage >16 ng/ml),
Uracilemia dosing results must be available before inclusion,
26. 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,
27. Known peripheral sensory neuropathy with functional impairment according exclusion
criteria n°9) prior to first treatment, according to the Summary of product
characteristics (SmPC) of oxaliplatin,
28. Known potentially serious infection, according to the SmPC of 5-FU
29. Has clinically significant active heart disease or myocardial infarction within 6
months given the cardiotoxicity of 5-FU, according to the SmPC of 5-FU,
30. Known history of hypersensitivity to 5-FU, oxaliplatin, or leucovorin, or to any of
their excipients, according to the Summary of Product Characteristic (SmPCs) of
these products.
Exclusion criteria related to geographical, social, and legal issues
31. Impossibility of submitting to the medical follow-up of the study for geographical,
social, or psychiatric illness,
32. Patient under a legal protection regime (guardianship, curatorship, judicial
safeguard) or administrative decision or incapable of giving his/her consent.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Clinique Sainte Catherine
Address:
City:
Avignon
Country:
France
Status:
Recruiting
Contact:
Last name:
Clemence TOULLEC, MD
Facility:
Name:
Centre Hospitalier Universitaire Jean Minjoz
Address:
City:
Besançon
Country:
France
Status:
Recruiting
Contact:
Last name:
Angelique VIENOT, MD
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux
Country:
France
Status:
Recruiting
Contact:
Last name:
Simon PERNOT, MD
Facility:
Name:
Centre Hospitalier de Cholet
Address:
City:
Cholet
Country:
France
Status:
Recruiting
Contact:
Last name:
Thonas CENTRE HOSPITALIER DE CHOLET, MD
Facility:
Name:
Centre Hospitalier Universitaire Clermont Ferrand - Site Estaing
Address:
City:
Clermont-Ferrand
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Marine JARY, MD
Facility:
Name:
Centre Georges Francois Leclerc
Address:
City:
Dijon
Country:
France
Status:
Recruiting
Contact:
Last name:
Francois GHIRINGHELLI, MD
Facility:
Name:
Centre Hospitalier Universitaire Grenoble Alpes - Site Nord - Hopital Michallon
Address:
City:
La Tronche
Country:
France
Status:
Recruiting
Contact:
Last name:
Gael ROTH, MD
Facility:
Name:
Centre Hospitalier Universitaire de Lille
Address:
City:
Lille
Country:
France
Status:
Recruiting
Contact:
Last name:
Anthony TURPIN, MD
Facility:
Name:
Catégorie centre CLCC
Address:
City:
Lyon
Country:
France
Status:
Recruiting
Contact:
Last name:
Clelia COUTZAC, MD
Facility:
Name:
Centre Hospitalier Universitaire Nantes - Hopital Hotel Dieu
Address:
City:
Nantes
Country:
France
Status:
Recruiting
Contact:
Last name:
Dahna COUPEZ, MD
Facility:
Name:
Hopital Saint Antoine
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Romain COHEN, MD
Facility:
Name:
Hopital Saint-Louis
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Thomas APARICIO, MD
Facility:
Name:
Institut Mutualiste Montsouris
Address:
City:
Paris
Country:
France
Status:
Recruiting
Contact:
Last name:
Emilie SOULARUE, MD
Facility:
Name:
Centre Hospitalier Universitaire de Poitiers - Hopital de La Miletrie
Address:
City:
Poitiers
Country:
France
Status:
Recruiting
Contact:
Last name:
David TOUGERON, MD
Facility:
Name:
Centre Hospitalier Universitaire Reims Hopital Robert Debre
Address:
City:
Reims
Country:
France
Status:
Recruiting
Contact:
Last name:
Olivier BOUCHE, MD
Facility:
Name:
Centre Hospitalier Saint-Malo
Address:
City:
Saint-Malo
Country:
France
Status:
Recruiting
Contact:
Last name:
Romain DESGRIPPES, MD
Facility:
Name:
Centre Hospitalier Universitaire Tours - Hopital Trousseau
Address:
City:
Tours
Country:
France
Status:
Recruiting
Contact:
Last name:
Elise DOUARD TOURNET, MD
Facility:
Name:
Hopital Paul Brousse
Address:
City:
Villejuif
Country:
France
Status:
Recruiting
Contact:
Last name:
Pascal Hammel, MD
Start date:
July 2024
Completion date:
March 2029
Lead sponsor:
Agency:
GERCOR - Multidisciplinary Oncology Cooperative Group
Agency class:
Other
Source:
GERCOR - Multidisciplinary Oncology Cooperative Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06253611
