Peritoneum is among the most common sites of metastases in gastric cancer. Systemic chemotherapy is the current standard for peritoneal carcinomatosis (PC), although, the treatment results remain extremely poor. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a modern treatment modality for PC, that 1) optimize the drug distribution by applying an aerosol rather than a liquid solution; and 2) apply increased intraperitoneal hydrostatic pressure to increase drug penetration to the target. Despite some encouraging preliminary results for PIPAC efficacy, it is still an investigational treatment. Furthermore, only very limited data exist for bidirectional treatment, which includes a combination of systemic chemotherapy and PIPAC. Thus, this study will investigate the feasibility of PIPAC and systemic chemotherapy combination for gastric cancer patients with peritoneal metastases.
This open-label, single-arm feasibility study will be conducted at two major gastrointestinal cancer treatment centers in Lithuania and will include 37 participants. Gastric cancer patients diagnosed with a synchronous or metachronous peritoneal carcinomatosis based on a clinical, radiological, cytological, and histological examination will be considered for enrollment. Thirty-seven patients willing to participate and meeting the enrollment criteria will be scheduled for the experimental treatment. Three cycles of 1st line palliative systemic chemotherapy will be administered every 28 days and PIPAC with cisplatin 10,5 mg/m2 and doxorubicin 2,1 mg/m2 will be utilized 14 days after each of the systemic chemotherapy cycles. After the 3rd PIPAC procedure patients will be re-assessed and discussed at multidisciplinary team meetings. In case of downstaging patients will be considered for radical gastrectomy±cytoreductive surgery; others for further systemic therapy. All patients will be followed up for 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Each course of combined treatment will start with PIPAC (a pressurized aerosol containing cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 diluted in NaCl 0.9% applied through the nebulizer inside the abdominal cavity during laparoscopy). Fourteen days afterward 2 cycles of systemic FOLFOX chemotherapy will be applied within 28 days. The interval between combined treatment courses will be 14 days.
Nationa Cancer Institute
Vilnius, Vilniaus, Lithuania
Vilnius University hospital Santaros Klinikos
Vilnius, Vilniaus, Lithuania
Objective tumor response according to RECIST v 1.1 after second PIPAC
Objective tumor response according to RECIST v 1.1 in CT scan performed 1 week after second PIPAC procedure
Time frame: Day 7 after second PIPAC procedure (an average of 8 weeks after start of the study)
Objective tumor response according to RECIST v 1.1
Objective tumor response according to RECIST v 1.1 in CT scan performed 1 week after third PIPAC procedure
Time frame: Day 7 after third PIPAC procedure (an average of 15 weeks after start of the study)
Compliance to treatment
Proportion of patients able to receive all anticipated treatment (3 PIPACs and 6 cycles of FOLFOX)
Time frame: Through study completion, an average of 28 months
Postoperative complication assessed by Clavien-Dindo score
The number of patients with postoperative complications, defined and graded according to Clavien-Dindo classification
Time frame: Through study completion, an average of 28 months
Peritoneal carcinomatosis index and histological regression according to peritoneal regression grading score (PRGS).
A pathologist blinded to clinical outcomes will evaluate histological tumor response using the Peritoneal Regression Grading Score (PRGS): 1-Complete regression without cancer cells; 2-higher response with prevalence of regressive phenomena and only a few residual cancer cells - PRGS; 3-minor response with prevalence of residual cancer cells and poor regressive phenomena; 4-no response to therapy without regressive phenomena. A patient will be considered a responder if any reduction in the PRGS during subsequent biopsies will be recorded.
Time frame: Through study completion, an average of 28 months
Ascites volume
The volume of ascites recorded at every PIPAC procedure.
Time frame: Through study completion, an average of 28 months
Tumor markers
Ca19-9, carcinoembryonic antigen (CEA), Ca72-4 plasma levels measured at different time points.
Time frame: Through study completion, an average of 28 months
Quality of life by EORTC questionnaires
Quality of life by EORTC questionnaires measured at different time points.
Time frame: Through study completion, an average of 28 months
Overall survival
Time from start of the treatment to death
Time frame: From treatment start to death, assessed up to 24 months
Progression-free survival
Time from start of the treatment to progression of the disease
Time frame: From treatment start to death, assessed up to 24 months
Adverse events of chemotherapy drugs
The number of patients with toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 during the study period
Time frame: Through study completion, an average of 28 months
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