Clinical trial NCT06759064: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer of Stomach, Adenocarcinoma
Ascites, Malignant
Keywords: gastric cancer
malignant ascites
Immune checkpoint inhibitors
zoledronic acid
intraperitoneal injection
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2025-01-06
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Rates of Adverse events according to CTCAE 5.0 in the Phase Ib stage
timeFrame: 3 months after the last treatment
measure: 4-week objective response rate
timeFrame: 4 weeks after last treatment
Secondary outcomes:
measure: Rates of Adverse events according to CTCAE 5.0 in overall subjects
timeFrame: 3 months after the last treatment
measure: 8-week objective response rate
timeFrame: 8 weeks after treatment
measure: Time for ascites control
timeFrame: 1 year
measure: Immune cell changes
timeFrame: 4 weeks
measure: Tumour markers
timeFrame: 8 weeks
measure: Quality of Life Assessment
timeFrame: 1 year
Other outcomes:
Locations:
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
Study officials:
References: