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

Phase 1

Recruiting

• Conditions: Cancer of Stomach, Adenocarcinoma; Ascites, Malignant
• Interventions: Drug: zoledronic acid plus Sintilimab intraperitoneal injection

• Registration Number: NCT06759064
• Lead Sponsor: Qilu Hospital of Shandong University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-09-12
• Status Verified: 2024-12
• Study First Submitted: 2024-12-10
• Study First Submitted QC: 2024-12-29
• Last Update Submitted: 2024-12-29
• Study First Posted: 2025-01-06
• Last Update Posted: 2025-01-06
• Primary Completion: 2025-02-01
• Study Completion: 2025-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
zoledronic acid plus Sintilimab intraperitoneal injection therapy arm	zoledronic acid plus Sintilimab intraperitoneal injection	patients will receive zoledronic acid 0.5-1mg plus Sintilimab 1.0mg/kg intraperitoneal injection

Primary Outcome Measures

Name	Time	Method
Rates of Adverse events according to CTCAE 5.0 in the Phase Ib stage	3 months after the last treatment	Adverse events were graded and recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. A general physical examination, measurement of vital signs, laboratory safety evaluation, and documentation of relevant adverse events were performed at each visit during the treatment period.
4-week objective response rate	4 weeks after last treatment	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

Secondary Outcome Measures

Name	Time	Method
Time for ascites control	1 year	If PD was judged and ascites was not re-punctured and drained, the time of this follow-up visit was used as the time of ascites control; if the patient had undergone puncture and drainage prior to the follow-up visit due to intolerance of ascites symptoms, the time of re-puncture was used as the time of ascites control.
Immune cell changes	4 weeks	Immune cell changes in ascites
Tumour markers	8 weeks	carcinoembryonic antigen (CEA), CA19-9, CA72-4
Quality of Life Assessment	1 year	A quality of life score (QOL) for oncology patients was used. The quality of life score (QOL) of oncology patients contains 12 dimensions, including appetite, spirit, sleep, fatigue, pain, family understanding and cooperation, colleagues' understanding and cooperation (including leadership), own knowledge of cancer, attitude towards treatment, daily life, side effects of treatment, and facial expression, with the highest score of 5 and the lowest score of 1 for each dimension. Quality of life grading: Quality of life is scored out of 60, with 51-60 for good, 41-50 for better, 31-40 for average, 21-30 for poor, and \<20 for very poor quality of life.
Rates of Adverse events according to CTCAE 5.0 in overall subjects	3 months after the last treatment	Adverse events were graded and recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. A general physical examination, measurement of vital signs, laboratory safety evaluation, and documentation of relevant adverse events were performed at each visit during the treatment period.
8-week objective response rate	8 weeks after treatment

Trial Locations

Locations (1)

Qilu Hospital of Shandong University; 🇨🇳 Jinan, Shandong, China