Phase II Study of Neoadjuvant Immune Checkpoint Inhibitor in Patients with Resectable Gastrointestinal Cancers
- Conditions
- Neoplasms
- Registration Number
- KCT0004253
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 48
To be eligible for this study, subjects must meet all of the following criteria:
Disease-related inclusion criteria
1)Histologically confirmed localized gastric adenocarcinoma, esophageal squamous cell carcinoma, hepatocellular carcinoma or clinically diagnosed hepatocellular carcinoma according to American Association for the Study of Liver Disease (AASLD) guidelines.
2)Curatively resectable gastric adenocarcinoma, esophageal squamous cell carcinoma or hepatocellular carcinoma
Gastric adenocarcinoma: clinical stage =T2 or regional lymph node metastasis (N+) (AJCC 8th)
Esophageal squamous cell carcinoma: clinical stage =T1b or N+ (AJCC 8th)
Hepatocellular carcinoma: a single hepatocellular carcinoma limited to liver or 3 or less hepatocellular carcinoma limited to liver without invasion to main portal trunk
3)The requirements for hematology, blood chemistry, and functionality in major organs are as follows (should be met within 7 days prior to the first administration of investigational medicinal product):
Absolute neutrophil count =1,000/µL
Platelets count =75,000/µL
Total bilirubin =1.5 × Upper limit of Normal (ULN) (subjects with Gilbert syndrome: bilirubin = 3.0 × ULN)
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 2.5 × ULN; alkaline phosphatase = 2.5 × ULN
Serum creatinine =1.5 × ULN or creatinine clearance =50 mL/minute (creatinine clearance is first calculated by the formula of Cockcroft-Gault and in case of the value less than 50 mL/min, by collecting and examining 24-hour urine the subjects with the creatine clearance =50 mL/minute can be enrolled) (Refer to Supplement 1).
Urine protein-creatinine ratio (UPC) =1 (in case of UPC >1, by collecting and examining 24-hour urine the subjects with the urine protein <2 g/day can be enrolled)
Also, in case of hepatocellular carcinoma, liver function with Child-Pugh grade A (Refer to Supplement 2) and encephalopathy grade 0.
4)Measurable or evaluable lesion(s) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Refer to Supplement 3).
5)Tumor tissue specimen, classified as appropriate for biomarker analysis, must be provided (in case of hepatocellular carcinoma, subjects, without tissue specimen prior to the administration of investigational medicinal product, are allowed for enrollment into the study).
General inclusion criteria
6)Aged = 19 years old
7)Eastern Cooperative Oncology Group (ECOG) performance status 0-1
8)Signed informed consent form
9)In the case of fertility men and women, Those who should be using adequate contraceptive measures while on study drug and for 3months following the last dose of study drug.
If any of the following criteria is met, subjects will be excluded.
Tumor-related exclusion criteria
1)Curatively unresectable or metastatic disease
2)Any prior treatment for gastric adenocarcinoma, esophageal squamous cell carcinoma or hepatocellular carcinoma. However, in case of hepatocellular carcinoma, it is possible for subjects to be enrolled into the study only if the treatment for local lesion was carried out =6 months ago and the treated area showed disease progression, or a curatively resectable new lesion has occurred outside the previously treated area, and other inclusion/exclusion criteria are met.
3)Patients with history of other cancers within three years prior to the study treatment. However, patients with other cancers with less influence on their prognosis such as carcinoma in situ or thyroid papillary carcinoma, in the opinion of the investigator, can be enrolled into the study.
4)History of hepatic encephalopathy.
5)Clinically significant ascites defined as follows:
When screening, the physical examination reveals ascites or
Previous ascites that required treatment and continuous prevention or current ascites that require treatment.
Investigational medicinal product-related exclusion criteria
6)History of active autoimmune disease with systematic treatment (i.e. immunomodulator, corticosteroid, or immunosuppressant) required within the past 2 years. Replacement therapy (e.g. physiological corticosteroid replacement therapy due to dysfunction of thyroxine, insulin, adrenal gland, or pituitary gland, etc.) is not regarded as a form of systematic treatment and would be allowed.
7)Diagnosis of immunodeficiency or within 7 days prior to the first administration of investigational medicinal product treatments with chronic systematic steroids (the dose equivalent to 10 mg/day of prednisone) or immunosuppressive therapy in any other forms are not permitted.
8)History of non-infectious interstitial pneumonia requiring treatment of steroids or currently diagnosed.
9)Any prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or other antibodies or drugs, specifically target co-stimulatory T cells or immune checkpoint pathways.
General exclusion criteria
10)Active infection with systematic treatment required.
11)From the viewpoint of the investigator, medical conditions, treatments, or laboratory test abnormalities that are likely to cause confusion in clinical trial results, or that are likely to interfere with subjects’ participation throughout the entire study, or that are not considered to be in the best interests of the subjects.12)Positive urine test or blood pregnancy test in childbearing females within 7 days prior to the first administration of investigational medicinal product.
13)Pregnant or lactating, or during the scheduled study period of 90 days after the final administration of investigational medicinal product, subjects have a plan to have conception.
14)Diagnosis of symptomatic congestive heart failure (i.e. New York Heart Association Classification class II and up) or history of clinically significant heart arrhythmia that requires other antiarrhythmic drugs other than beta blockers and digoxin, or currently diagnosed or occurrence of conduction disorders (atrial fibrillation, paroxysmal supraventricular tachycardia are exceptional) within 6 months prior to the study, active coronary artery diseases, unstable angina, new occurrence of angina within 3 months before enrollment of
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Rate of pathology (major pathologic response rate <10%)
- Secondary Outcome Measures
Name Time Method Feasibility and safety of preoperative IMC-001