||A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
| Protocole ID
| ClinicalTrials.gov ID
| Type(s) de cancer
||Maladie avancée ou métastatique
| Type étude
||Zolbétuximab avec CAPOX
CISSS DU BAS-SAINT-LAURENT
HOPITAL REGIONAL DE RIMOUSKI
150 av. Rouleau, Rimouski, QC, G5L 5T1
| Investigateur(trice) principal(e)
Dre Sophie Savary Bélanger
418-724-3000 poste 8029
|| Actif en recrutement
| Critètes d'éligibilité
A female subject is eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin (βhCG) and a demonstrated non-pregnant status through additional testing are eligible) and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for 6 months after the final study treatment administration
- Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
- Female subject must not donate ova starting at screening and throughout the study period, and for 6 months after the final study treatment administration.
A male subject with female partner(s) of childbearing potential:
- must agree to use contraception during the treatment period and for 6 months after the final study treatment administration.
- A male subject must not donate sperm during the treatment period and for 6 months after the final study treatment administration.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study treatment administration.
- Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
- Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to the first dose of study treatment.
- Subject has measurable disease according to RECIST 1.1 within 28 days prior to the first dose of study treatment. For subjects with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
- Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing.
- Subject has a HER2-negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
- Subject has ECOG performance status 0 or 1.
- Subject has predicted life expectancy ≥ 12 weeks.
Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. In case of multiple central laboratory data within this period, the most recent data should be used to determine eligibility.
- Hemoglobin (Hb) ≥ 9 g/dl. NOTE: subject must not have received any growth factor or blood transfusions within 14 days prior to the hematology values obtained at screening. Subjects requiring transfusions to meet eligibility criteria are not eligible.
- Absolute Neutrophil Count (ANC) ≥ 1.5x10^9/L
- Platelets ≥ 100x10^9/L
- Albumin ≥ 2.5 g/dL
- Total Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
- Estimated creatinine clearance ≥ 30 mL/min
- Prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
| Critètes d'exclusion
- Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to the first dose of study treatment.
- Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma unless the radiotherapy was completed > 28 days prior to the first dose of study treatment. Subject who received palliative radiotherapy to peripheral bone metastases ≥ 14 days prior to first dose of study treatment and has recovered from all acute toxicities is eligible.
- Subject has received treatment with herbal medications or other treatments that have known antitumor activity within 28 days prior to first dose of study treatment.
- Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to first dose of study treatment. Subject using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone) or a single dose of systemic corticosteroids is eligible.
- Subject has received other investigational agents or devices within 28 days prior to first dose of study treatment.
- Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
- Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
- Subject has prior severe allergic reaction or intolerance to any component of CAPOX.
- Subject has known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Subject has gastric outlet syndrome or persistent/recurrent vomiting.
- Subject had recent gastric bleeding and/or is symptomatic with proven gastric ulcers that excludes the subject from participation.
- Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or hepatitis C infection. For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded. Subjects with positive serology but negative hepatitis C virus (HCV) ribonucleic acid (RNA) test results are eligible.
- Subject has an active autoimmune disease that has required systemic treatment within the past 2 years.
- Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to first dose of study treatment.
Subject has significant cardiovascular disease, including any of the following:
- Congestive heart failure (defined as New York Heart Association [NYHA] Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident (CVA), or hypertensive crisis within 6 months prior to administration of first dose of study treatment;
- History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes);
- QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects;
- History or family history of congenital long QT syndrome
- Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to first dose of study treatment are eligible.)
- Subject has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Subject has known peripheral sensory neuropathy > grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
Subject has had a major surgical procedure ≤ 28 days prior to the first dose of study treatment.
- Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to the first dose of study treatment.
- Subject has psychiatric illness or social situations that would preclude study compliance.
- Subject has another malignancy for which treatment is required.
- Subject has any concurrent disease, infection, or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.