Last updated: November 7, 2023
Sponsor: Fudan University
Overall Status: Active - Recruiting
Phase
2
Condition
Adenocarcinoma
Digestive System Neoplasms
Gastric Cancer
Treatment
Chemotherapy
Anti-PD-1 monoclonal antibody
Local ablative therapies
Clinical Study ID
NCT06121700
FDRT-2022-260-2977
Ages 18-75 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
- Histopathologically confirmed adenocarcinoma of stomach (G) or gastroesophagealjunction (GEJ) (excluding Siewert type I).
- Limited metastatic status of disease.
- At least one evaluable lesion in CT/MRI according to RESIST 1.1 is required.
- The status of HER2 is clear.
- pMMR/MSS confirmed by immunohistochemistry or gene test.
- Male or female. Patient age ≥ 18 years and ≤ 75 years.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
- Physical state or organ function can tolerate the planned treatment of the studyprotocol, including systematic chemotherapy, immunotherapy with anti-PD-1 monoclonalantibody (mAb), primary lesion radiotherapy, metastatic lesion radiotherapy, andsurgical resection of primary and/or metastatic lesions.
- No previous surgery or antitumor therapies, including chemotherapy, radiotherapy, orimmunotherapy, were administered.
- Adequate hematological function: absolute neutrophil count (ANC) ≥ 1.5×109/L; plateletcount ≥ 100×109/L; hemoglobin level ≥ 90 g/L.
- Adequate hepatic function: total bilirubin ≤ 1.5×upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN incase of liver metastases; ALP ≤ 2.5×ULN; ALB ≥ 30 g/L.
- Adequate renal function: serum creatinine ≤ 1.5×ULN; creatinine clearance rate ≥ 60ml/min.
- Adequate coagulation function: INR/PT ≤ 1.5×ULN; APTT ≤ 1.5×ULN.
- TSH is within the normal range; if TSH is out of the normal range, FT3 and FT4 shouldbe investigated. If the test results of FT3/FT4 cannot be obtained, T3 and T4 can beaccepted. 13. If the level of T3/T4 is normal, the patients can be selected.
- Urine test: urine protein<2+; if the urine protein≥2+, the 24-hour urine proteinquantification must be≤1g.
- There is no serious concomitant disease, and the patient's life expectancy is morethan 6 months.
- Patients agree to sign written informed consent before recruitment.
- Patients are willing and able to follow the protocol during the study, includingreceiving treatment and scheduled follow-up and examination.
- Patients are willing to provide samples of blood and tissue.
- Female patients should not be pregnant or breast feeding.
- Female patients agree to take contraceptive measures during treatment and within 120days after the last dose of anti-PD-1 mAb or 180 days after the last use ofchemotherapy or radiotherapy. Definition of the limited metastatic disease:
- Retroperitoneal lymph node metastases (RPLM) only or at maximum one organ involvedwith or without RPLM.
- There is no peritoneal seeding on diagnostic laparoscopy (P0).
- The definition of RPLM includes but is not limited to para-aortal, intra-aorto-caval,parapancreatic or mesenteric lymph nodes. If the duodenum is invaded, retropancreaticnodes are not regarded as M1.
- The definition of single organ metastasis in the study is as follows: a) Liver:maximum of 5 metastatic lesions that are potentially resectable and the metastasesshould be limited to one lobe and not involve important blood vessels or bile ducts.b) Lung: unilateral involvement, potentially resectable. c) Ovary: uni- or bilateralKrukenberg tumors in the absence of macroscopic peritoneal carcinomatosis. d) Adrenalgland: uni- or bilateral metastases. e) Extra-abdominal lymph node metastases, such assupraclavicular or cervical lymph node involvement. f) Bone: localized boneinvolvement (defined as being within one radiation field).
- Other metastatic disease locations are considered, limited by the investigator andconfirmed by the multidisciplinary team (MDT).
Exclusion
Exclusion Criteria:
- Patients who have previously received surgery, chemotherapy, radiotherapy orimmunotherapy for gastric cancer.
- Patients have a history of cancer in the five years before enrollment except forsquamous or basal cell carcinoma of the skin that was effectively treated andsuperficial bladder cancer, cervical carcinoma in situ and breast cancer in situ thatwas treated by operation.
- Pregnant or lactating females or females planning to become pregnant or lactating.Women of childbearing age with a positive pregnancy test or without a pregnancy testin the baseline period. Menopausal women must have stopped menstruating for at least 12 months before being considered to have no chance of pregnancy.
- Patients who had sexual activity (with the possibility of childbirth) and wereunwilling to use contraception during the study period.
- Patients with a history of allergies to any drugs that may be used in this study,including chemotherapy drugs.
- History of allogeneic stem cell transplantation or organ transplantation.
- Vaccinated with live vaccine within 28 days before recruitment.
- Immunotherapy (interleukin, interferon, thymine) or other experimental treatment wasgiven 28 days before enrollment.
- History of anti-PD-1, PD-L1, PD-L2 or any other specific T-cell costimulation orcheckpoint pathway targeted therapy.
- History of using steroids (dose > 10 mg/d prednisone) or other systemicimmunosuppressive therapy within 14 days before recruitment, except for patientstreated with the following regimen: steroids used for hormone replacement (dose > 10mg/d prednisone); local application of steroids with little systemic absorption;short-term (≤ 7 days) use of steroids to prevent allergy or vomiting.
- Patients with weight loss of more than 20% within 2 months before recruitment.
- Uncontrolled systemic diseases, including diabetes, hypertension, etc.
- Uncontrollable pleural effusion, pericardial effusion, or ascites occurred within twoweeks before recruitment.
- Failure of important organs (heart, lung, liver, kidney, etc.).
- Moderate or severe renal injury [creatinine clearance ≤ 50 ml/min (according toCockcroft & Gault equation)], or SCR > ULN.
- Dipyrimidine dehydrogenase (DPD) deficiency.
- Patients with central nervous system (CNS) disorders or tumors, including brainmetastases, peripheral nervous system disorders or psychiatric diseases.
- Cerebrovascular accidents occurred within 6 months before recruitment.
- Patients with peripheral neuropathy of NCI-CTCAE grade 1, except for those withdisappearance of the deep tendon reflex.
- Patients with a known history of uncontrolled or symptomatic angina, uncontrolledarrhythmias and hypertension, congestive heart failure, cardiac infarction or cardiacinsufficiency within 6 months prior to study recruitment.
- Pulmonary embolism occurred within 28 days before enrollment.
- Patients who had the following history of pulmonary diseases: interstitial lungdisease, noninfectious pneumonia, pulmonary fibrosis, or acute lung disease.
- Patients with gastrointestinal bleeding or a high risk of bleeding within the first 2weeks of enrollment.
- Patients who experienced gastrointestinal perforation or fistula within 6 months priorto enrollment.
- Upper gastrointestinal obstruction, dysfunction or malabsorption syndrome may affectthe absorption of oral chemotherapy drugs.
- Patients who cannot swallow or take medication orally.
- Patients with a history of active autoimmune disease or refractory autoimmune disease.
- Severe chronic or active infections requiring systemic antibiotics, antifungal orantiviral therapy, including tuberculosis and AIDS.
- Known history of human immunodeficiency virus (HIV) infection.
- Patients with untreated chronic hepatitis B or HBV-DNA exceeding 500 IU/ml or HCV-RNApositive.
- Alcohol/drug abuse and medical, psychological or social conditions may interfere withpatients' participation in the study or have an impact on the evaluation of the studyresults.
Study Design
Total Participants: 55
Treatment Group(s): 8
Primary Treatment: Chemotherapy
Phase: 2
Study Start date:
January 01, 2023
Estimated Completion Date:
December 31, 2027
Connect with a study center
Fudan University Shanghai Cancer Center
Shanghai,
ChinaActive - Recruiting
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