Intraperitoneal Immune Checkpoint Inhibitors and Zoledronic Acids for Gastric Cancer Malignant Ascites

Official title

Efficacy and Safety of Intraperitoneal Immune Checkpoint Inhibitors and Zoledronic Acids in Gastric Cancer Malignant Ascites: a Phase I/II Clinical Study (IPIZA)

Overview

This study is to evaluate the safety and efficacy of intraperitoneal injection of immune checkpoint inhibitor combined with zoledronic acid for the treatment of malignant ascites in gastric cancer. This study is a phase Ib/II clinical study to evaluate the safety and efficacy of intraperitoneal injection of immune checkpoint inhibitors in combination with zoledronic acid in the treatment of malignant ascites in gastric cancer, which consists of two phases, firstly, the phase Ib safety study, which adopts the '3+3' drug-escalation experimental design, and after determining the safe and tolerable dose, it will proceed to the second part of the phase II efficacy study. The Phase II study was designed by Simon's two-stage approach to evaluate the efficacy of immune checkpoint inhibitors in combination with zoledronic acid in the treatment of malignant ascites in gastric cancer.

Interventions

• Drug zoledronic acid plus Sintilimab intraperitoneal injection
  At D-5\~D-1, drain the ascites by placing a tube in the abdominal cavity first, try to drain the ascites as much as possible according to the clinical routine, and record the amount of drainage.D1, D8, D15, D22 start the first immunocheckpoint inhibitor combined with zoledronic acid treatment, try to drain the ascites first, calculate the amount of drugs according to the patient's body weight, and then dissolve the corresponding dosage of immunocheckpoint inhibitor and zoledronic acid in 100 ml

Primary outcome measures

• Dose-limiting toxicity (DLT) or maximal tolerance dose (MTD) in the Phase Ib stage [Time frame: 28 days after the last treatment]
• Objective response rate [Time frame: 4 weeks after last treatment]

Secondary outcome measures (4)

• Rates of Adverse events according to CTCAE 5.0 in overall subjects [Time frame: 3 months after the last treatment]
• Time for ascites control [Time frame: 1 year]
• Immune cell changes [Time frame: 4 weeks]
• Quality of Life Assessment [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

• Gastric adenocarcinoma diagnosed pathologically;
• Malignant ascites confirmed by ascites cytology;
• Presence of ascites confirmed by CT with ascites graded as 2nd and 3rd degree (EASL guidelines and ICA consensus);
• Those aged 18-75 years;
• Patients who had not undergone local administration of drugs in the abdominal cavity and systemic immunotherapy within the previous 4 weeks;
• Vital signs are stable, Karnofsky score (≥70), and expected survival time is >3 months;
• Normal bone marrow haematopoietic function, blood routine: HGB ≥90g/L, WBC ≥2.5×10\^9/L (NEU ≥1.5×10\^9/L), PLT ≥90×10\^9/L;
• Normal coagulation function without bleeding tendency (International normalised ratio of prothrombinogen INR<1.5);
• Liver function: total bilirubin ≤1.5 times the upper limit of normal (ULN); AST and ALT ≤2 times the upper limit of normal (ULN) (or ≤5 times the upper limit of normal (ULN) if the abnormalities are mainly due to tumour infiltration);
• Renal function: Cr ≤1.5 times the upper limit of normal (ULN) or creatinine clearance ≥60mL/min.

Exclusion criteria

• Non-malignant ascites (e.g., portal hypertension ascites or infected ascites);
• Presence of contraindications to immunotherapy (including long-term hormone use, history of radiation pneumonitis, radiation hepatitis, radiation enteritis, etc.);
• Combination of other serious cardiopulmonary diseases that affect the treatment, etc;
• Patients with extensive abdominal adhesions; encapsulated peritoneal fluid; history of intestinal obstruction; and malignant patients with extensive distant metastases in the terminal stage;
• Women who are breastfeeding, pregnant, or preparing for pregnancy;
• Patients with plasma albumin (ALB) <30 g/L and severe hypoproteinemia;
• Patients with known hypersensitivity to components of the test drug or its analogues;
• Patients with other severe, acute or chronic diseases that may interfere with the interpretation of the study results and who, in the judgement of the investigator, are unsuitable for participation in the clinical trial;
• Patients with cognitive dysfunction, or poor treatment compliance as judged by the investigator;
• Participants in other clinical trials within 4 weeks;
• Combination of other malignancies;
• Those who, in the opinion of the investigator, are not suitable for participation in the clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Qilu Hospital of Shandong University — Jinan

Identifiers

NCT: NCT06759064 · IPIZA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗