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

NCT06759064 | Recruiting Phase 1

• 1 other identifier: IPIZA
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer of Stomach, Adenocarcinoma; Ascites, Malignant

Keywords

gastric cancer; malignant ascites; Immune checkpoint inhibitors; zoledronic acid; intraperitoneal injection

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT) or maximal tolerance dose (MTD) in the Phase Ib stage

  Side effects of drug or treatment that are serious enough (e. g. ≥Grade 3 non-hematologic toxicity according to CTCAE 5.0 in ≥1/3) to prevent an increase in dose or level of that treatment. The MTD is defined as the previous dose level.

  28 days after the last treatment

• Objective response rate

  Complete remission (CR): complete resolution of ascites and maintained for more than 4 weeks; complete disappearance of all target lesions; Partial remission (PR): the amount of CT-measured ascites decreased by more than 50% compared to pretreatment and the amount of ascites withdrawn again was less than 1/2 of the previous withdrawal and was maintained for more than 4 weeks; the sum of the diameters of all measurable target lesions was ≥30% below baseline; Objective Response Rate（ORR） = CR + PR

  4 weeks after last treatment

Secondary Outcomes (4)

• Rates of Adverse events according to CTCAE 5.0 in overall subjects

  3 months after the last treatment

• Time for ascites control

  1 year

• Immune cell changes

  4 weeks

• Quality of Life Assessment

  1 year

Study Arms (1)

zoledronic acid plus Sintilimab intraperitoneal injection therapy arm

EXPERIMENTAL

patients will receive zoledronic acid 0.5-1mg plus Sintilimab 1.0mg/kg intraperitoneal injection

Drug: zoledronic acid plus Sintilimab intraperitoneal injection

Interventions

zoledronic acid plus Sintilimab intraperitoneal injection DRUG

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 of saline and inject them into the abdominal cavity respectively, and then inject another 100 ml of saline according to the patient's tolerance. The corresponding dose of immune checkpoint inhibitor and zoledronic acid was dissolved in 100 ml of saline and injected into the abdominal cavity.

zoledronic acid plus Sintilimab intraperitoneal injection therapy arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma; Ascites

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: January 6, 2025
• Study Start: September 12, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)