Phase 1 study of modified FOLFOXIRI in combination with molecular targeted therapy and immune checkpoint inhibitors for advanced gastric cancer (G-FOLFOXIRI)
G-FOLFOXIRI study
Masuishi Toshiki
Aichi Cancer Center Hospital
1-1,Kanokoden,Chikusa-ku,Nagoya,Aichi
+81-52-762-6111
tmasuishi@aichi-cc.jp
Ishizuka Yasunobu
Aichi Cancer Center Hospital
1-1,Kanokoden,Chikusa-ku,Nagoya,Aichi
+81-52-762-6111
y.ishizuka@aichi-cc.jp
Recruiting
Jan. 20, 2025
Mar. 03, 2025
78
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1)Patients have given written informed consent.
2)The age of patients on registration date is 18 years or older.
3)Patients have diagnosed with histologically adenocarcinoma (general type).
4)No signs of intestinal obstruction are observed.
5)The patients have unresectable advanced or recurrent gastric cancer.
6)The presence or absence of measurable lesions is not a criterion for inclusion.
7)No prior history of chemotherapy for gastric cancer.
8)No prior history of treatment with oxaliplatin.
9)ECOG Performance Status (PS) is 0-1.
10)The latest laboratory results within 7 days prior to enrollment meet all following criteria
(1) Neutrophil count>=1,500/mm3
(2) Hemoglobin >=8.0 g/dL (with no history of blood transfusion within the 7 days prior to the blood test for enrollment)
(3) Platelet count>=100,000/mm3
(4) Total bilirubin level =<1.5 mg/dL
(5) Aspartate aminotransferase (AST, GOT)=<100 IU/L
(6) Alanine aminotransferase (ALT, GPT)=<100 IU/L
(7) Serum creatinine =<1.5 mg/dL patients with a serum creatinine >1.5 mg/dL may be eligible if the creatinine clearance (CCr) is >=20 mL/min.
NIVO Cohort
1) HER2-negative or HER2 status is indeterminate.
ZOL Cohort
1) HER2-negative or HER2 status is indeterminate.
2) CLDN18.2-positive.
Tmab Cohort
1) HER2-positive.
Tmab+Pembro Cohort
1)HER2-positive.
2)PD-L1 CPS>=1
1)Patients with concurrent cancer requiring treatment
2)Patients with symptomatic metastasis to the central nervous system (brain, spinal cord, or meninges)
3) Patients with ascites or pleural effusion requiring drainage
4)T Patients with a localized or systemic active infection that requires intervention
5) Patients with deemed unsuitable for enrollment due to a psychiatric disorder that could affect clinical trial participation
6) Patients with any of the following complications:
(1) Interstitial pneumonia/pulmonary fibrosis
(2) Positive for HBs antigen or HBV-DNA (patients on antiviral therapy for more than 1 week are eligible)
(3) Grade 2 or higher peripheral sensory neuropathy
7)Patients have undergone any of the following surgeries prior to treatment in this study:
(1) Major surgery involving resection or anastomosis of hollow organs within 14 days before the scheduled start date of study treatment, including laparotomy or laparoscopic surgery.
(2) Surgery involving a colostomy, exploratory laparotomy, or diagnostic laparoscopy within 7 days before the scheduled start date of study treatment.
8)Patients with a history of myocardial infarction or unstable angina within the last 6 months
9)Patients are pregnant, breastfeeding, possibly pregnant, or does not intend to use contraception
10)Patients with other significant medical abnormalities as judged by the investigator
NIVO Cohort
1) Patients who require systematic therapy including corticosteroid > 10 mg/day or other immunosuppressive agent within 14 days before registration.
2)Patients have a history of receiving anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibodies, or any other antibody or drug specifically targeting T-cell co-stimulatory or checkpoint pathways.
ZOL Cohort
1)Patients have a history of receiving anti-CLDN18.2 antibodies or other antibodies or drugs specifically targeting CLDN18.2.
Tmab Cohort
1)Patients have a history of receiving anti-HER2 antibodies or other antibodies or drugs specifically targeting HER2.
2)Patient's left ventricular ejection fractions are below 50% on echocardiography within 28 days prior to enrollment.
Tmab+Pembro Cohort
1)Patients who require systematic therapy including corticosteroid > 10 mg/day or other immunosuppressive agent within 14 days before reg istration.
2)Patients have a history of receiving anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antib odies, or any other antibody or drug specifically tar geting T-cell co-stimulatory or checkpoint pathways.
3)Patients have a history of receiving anti-HER2 antibodies or other antibodies or drugs specifically targeting HER2.
4)Patient's left ventricular ejection fractions are bel ow 50% on echocardiography within 28 days prior to enrollment.
18age old over
No limit
Both
gastric cancer
NIVO Cohort (mFOLFOXIRI+Nivolumab)
Nivolumab 240mg/body Day1
Irinotecan 150mg/m2 Day1 or 120mg/m2 Day1
Oxaliplatin 85mg/m2 Day1
Levofolinate 200mg/m2 Day1
Fluorouracil 2400mg/m2 Day1-3 (46 hours)
every two weeks
ZOL Cohort (mFOLFOXIRI+Zolubetuximab)
Zolubetuximab 800mg/m2 Day1(first cycle) 400mg/m2 Day1 (after second cycle)
Irinotecan 150mg/m2 or 120mg/m2 Day1 or Day2
Oxaliplatin 85mg/m2 Day1 or Day2
Levofolinate 200mg/m2 Day1 or Day2
Fluorouracil 2400mg/m2 Day1-3 or Day2-4 (46 hours)
every two weeks
Tmab Cohort (mFOLFOXIRI+Trastuzumab)
Trastuzumab 6mg/kg Day1(first cycle) 4mg/kg Day1 (after second cycle) every two weeks
Irinotecan 150mg/m2 Day1 or 120mg/m2 Day1
Oxaliplatin 85mg/m2 Day1
Levofolinate 200mg/m2 Day1
Fluorouracil 2400mg/m2 Day1-3 (46 hours)
every two weeks
or
Trastuzumab 8mg/kg Day1(first cycle) 6mg/kg Day1(after second cycle) every three weeks
Irinotecan 150mg/m2 Day1 or 120mg/m2 Day1
Oxaliplatin 85mg/m2 Day1
Levofolinate 200mg/m2 Day1
Fluorouracil 2400mg/m2 Day1-3 (46 hours)
every two weeks
Tmab+Pembro Cohort (mFOLFOXIRI+Trastuzumab+Pembrolizumab)
Pembrolizumab 200mg/body every three weeks or 4 00mg/body Day1 every six weeks
Trastuzumab 6mg/kg Day1 (first cycle) ,4mg/kg Day 1 (after second cycle) every two weeks or 8mg/kg D ay1 (first cycle) ,6mg/kg Day1 (after second cycle) e very three weeks
Irinotecan 150mg/m2 Day1 or 120mgm2 Day1 Oxaliplatin 85mg/m2 Day1
Levofolinate 200mg/m2 Day1
Fluorouracil 2400mg/m2 Day1-3 (46 hours)
Incidence of Dose-Limiting Toxicity (DLT)
1)Incidence of Adverse Events (AEs)
2)Relative dose intensity (RDI)
3)Response rate (RR)
4)Disease control rate (DCR)
5)Time to treatment failure (TTF)
6)Progression-free survival (PFS)
7)Duration of response (DoR)
8)Overall survival (OS)
Certified Review Board of Aichi Cancer Center in Hospital Management Bureau
