Phase II Study of Neoadjuvant Immune Checkpoint Inhibitor in Patients With Resectable Gastrointestinal Cancers(Neo-Chance Study)
Overview
- Phase
- Phase 2
- Intervention
- IMC-001
- Conditions
- Subjects With Resectable and Localized Gastric Cancer
- Sponsor
- Asan Medical Center
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Major pathologic response rate
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a phase II, open-label, prospective single-centered study. Subjects who meet the inclusion/exclusion criteria will be allocated to appropriate cohorts: 1) gastric cancer, 2) esophageal cancer and 3) hepatocellular carcinoma. Each cancer cohort group will be treated with two cycles of neoadjuvant immune checkpoint inhibitor of IMC-001 (1 cycle = 2 weeks) followed by curative resection and be followed up consecutively.
Detailed Description
This is a phase II, open-label, prospective single-centered study. Subjects who meet the inclusion/exclusion criteria will be allocated to appropriate cohorts: 1) gastric cancer, 2) esophageal cancer and 3) hepatocellular carcinoma. Each cancer cohort group will be treated with two cycles of neoadjuvant immune checkpoint inhibitor of IMC-001 (1 cycle = 2 weeks) followed by curative resection and be followed up consecutively. The sample size of the study is determined based on a major pathologic response rate (primary endpoint) and by using Simon's single stage design from the subjects who receive preoperative neoadjuvant therapy of IMC-001. In each cancer cohort group, the null and alternative response rates are assumed as 5% and 20%, respectively. This provides a power of 80% when calculating the difference between major pathologic response rates of 5% and 20% in two-tailed significance level of 0.153 (Type I error\[two-tailed\] of 15.3%). In order to reject the null hypothesis, at least two major pathological respondents are needed among 14 assessable subjects for each cancer cohort. After choosing the margin of safety as 10%, each cancer cohort will require 16 subjects and therefore a total of 48 subjects will be enrolled into the study.
Investigators
Sook Ryun Park
Associated professor
Asan Medical Center
Eligibility Criteria
Inclusion Criteria
- •\<Disease-related inclusion criteria\>
- •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.However, in cases of hepatic carcinoma that can be clinically diagnosed according to AASLD guideline, no biopsy is performed.
- •Curatively resectable gastric adenocarcinoma, esophageal squamous cell carcinoma or hepatocellular carcinoma
- •A. Gastric adenocarcinoma: clinical stage ≥T2 or regional lymph node metastasis (N+) (AJCC 8th)
- •B. Esophageal squamous cell carcinoma: clinical stage ≥T1b or N+ (AJCC 8th)
- •C. Hepatocellular carcinoma: a single hepatocellular carcinoma limited to liver or 3 or less hepatocellular carcinoma limited to liver without invasion to main portal trunk
- •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):
- •A. Absolute neutrophil count ≥1,000/μL
- •B. Platelets count ≥75,000/μL
- •C. Total bilirubin ≤1.5 × Upper limit of Normal (ULN) (subjects with Gilbert syndrome: bilirubin ≤ 3.0 × ULN)
Exclusion Criteria
- •\<Tumor-related exclusion criteria\>
- •Curatively unresectable or metastatic disease
- •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.
- •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.
- •History of hepatic encephalopathy.
- •Clinically significant ascites defined as follows:
- •A. When screening, the physical examination reveals ascites or
- •B. Previous ascites that required treatment and continuous prevention or current ascites that require treatment.
- •\<Investigational medicinal product-related exclusion criteria\>
- •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.
Arms & Interventions
Neoadjuvant IMC-001
Neoadjuvant immune check point inhibitor of IMC-001 in participants with resectable and localized gastric cancer, esophageal cancer, and hepatocellular carcinoma
Intervention: IMC-001
Outcomes
Primary Outcomes
Major pathologic response rate
Time Frame: After surgical resection within 28days
Evaluation of major pathologic response rate (a proportion of residual viable tumor cells \<10%) after administration of pre-operative immune checkpoint inhibitor IMC-001
Secondary Outcomes
- The safety and feasibility(Within 14 days after the end of Cycle 2 (+,- 4days))
- R0 resection rate(After surgical resection within 1 month)
- Clinical tumor response rate(1 month)
- Clnical disease control rate(1 month)
- Progression-free survival(2 years)
- Relapse-free survival(2 years)
- Overall survival(2 years)
- The rates and patterns of cancer progression/relapse(2 years)
- Patterns of cancer progression/relapse(2 years)