Clinical trial NCT05497739: Intraperitoneal Chemotherapy Guided by the Detection of DNA in Peritoneal Lavage Fluid in Patients With Gastric Cancer
Official title: Adjuvant Intraperitoneal Chemotherapy Guided by the Detection of Cancer Cell DNA in Peritoneal Lavage Fluid in Patients With Gastric Cancer: an Open-label, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastric Cancer
Keywords: Peritoneal metastasis
Personalized mutation assay
Cancer cell DNA
Intraperitoneal Chemotherapy
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2022-08-11
Enrollment: 68
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: Peritoneal metastasis is a major pattern of gastric cancer recurrence and predicts poor prognosis. In our previous study, we developed a next-generation sequencing technology to detect minimal residual cancer cells in peritoneal lavage fluid with a personalized assay profiling tumor-specific mutations in patients with gastric cancer. With this technology, we predicted all the cases that developed peritoneal metastasis in patients with pT4 disease with 100% sensitivity and 91% specificity. Based on this result, a prospective phase 2 clinical trial is designed to evaluate the efficacy of adjuvant intraperitoneal chemotherapy in patients with positive cancer cell DNA detected in peritoneal lavage fluid by our personalized tumor-specific mutation profiling assay.

Detailed description: Introduction:

Peritoneal metastasis is the most common pattern of gastric cancer recurrence and leads to rapid death. In a previous study, our team established a personalized method which could detect minimal cancer cell DNA in peritoneal lavage fluid with high sensitivity and specificity. We intend to perform a clinical trial to explore the efficacy of intraperitoneal chemotherapy on reducing the incidence of peritoneal metastases in patients with high risk defined by our personalized mutation detection method.

Methods and analysis:

This is a single-arm and single-center clinical trial. Sixty-eight patients with clinical T4 stage gastric cancers will be expected to be enrolled. During surgery, surgeons will wash upper abdominal cavity with 300-400 mL of normal saline before any manipulation of the tumor and collect about 200 mL peritoneal lavage fluid. Cancer cell DNA in peritoneal lavage fluid will be detected by next-generation sequencing using a personalized tumor-specific mutation profiling assay. Patients with positive peritoneal lavage fluid cancer cell DNA will receive adjuvant intraperitoneal chemotherapy in the second month since surgery, then followed by standard adjuvant systemic chemotherapy.

The primary endpoint is the incidence of peritoneal metastasis, and the secondary endpoints include peritoneal metastasis-free survival, disease-free survival (DFS), overall survival (OS), and the safety of intraperitoneal chemotherapy.

Ethics

This trial has been approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.

Eligibility criteria: Criteria:

1. Gastric adenocarcinoma confirmed by pathology (histology);
2. 18-75 years old;
3. Clinical T4 stage, no distant metastasis confirmed by CT and endoscopic ultrasonography (EUS), potentially curable by surgery;
4. Eastern Cooperative Oncology Group Performance Score 0 or 1;
5. Absolute neutrophil count at least 1.5×10\^9/L; platelets count at least 80×10\^9/L; hemoglobin at least 9 g/dL; serum creatinine or creatinine clearance no greater than 1.5 times upper normal limit (UNL); TSB no greater than 1.5 times ULN; AST (SGOT) and ALT (SGPT) no greater than 2.0 times ULN; albumin at least 3.0 mg/dL;
6. Provide tumor tissue, blood, and peritoneal lavage fluid samples;
7. Willing to accept long-term follow-up;
8. Ability to understand and sign a written informed consent before the trial procedure.

Exclusion Criteria

1. Currently participating in or receiving other clinical trial treatment;
2. Contraindications to investigational chemotherapy regimen including allergies to any of the chemotherapy medications;
3. Active infection requires systemic treatment;
4. Patients with poor compliance;
5. Patients who undergo non-curative surgery;
6. History of other malignant neoplasm within 5 years, except for early-stage skin cancer;
7. Pregnant or breast-feeding female;
8. Patients who have received neoadjuvant therapy.

Primary outcomes:
measure: The incidence of peritoneal metastasis
timeFrame: Two years after surgery.
Secondary outcomes:
measure: Peritoneal metastasis-free survival
timeFrame: Two years after surgery.
measure: Disease-free survival
timeFrame: Three years after surgery.
measure: Overall survival
timeFrame: Three years after surgery.
measure: The safety
timeFrame: Ninety days after surgery.
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital
state: Beijing
Study officials:
References: