PIPAC and FOLFOX for Gastric Cancer Peritoneal Cancer

Sponsor

Vilnius University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05644249

Collaborator

Vilnius University Hospital Santaros Klinikos (Other), National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Anticipated Duration (Months)

18.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Peritoneal Carcinomatosis	Drug: Combined Doxorubicin and Cisplatin Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic FOLFOX chemotherapy	N/A

Detailed Description

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 Design

Study Type:

Interventional

Anticipated Enrollment :

37 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) and Systemic Chemotherapy as a First-line Treatment for Gastric Cancer Peritoneal Metastases: Open-label, Single-arm, Multi-center Feasibility Study

Actual Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Oct 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental treatment Each patient will be scheduled for 3 courses of combined treatment: in total 3 PIPAC with cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 and 6 cycles of FOLFOX systemic chemotherapy.	Drug: Combined Doxorubicin and Cisplatin Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic FOLFOX chemotherapy 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. Other Names: PIPAC

Arm

Intervention/Treatment

Experimental: Experimental treatment

Each patient will be scheduled for 3 courses of combined treatment: in total 3 PIPAC with cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 and 6 cycles of FOLFOX systemic chemotherapy.

Drug: Combined Doxorubicin and Cisplatin Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic FOLFOX chemotherapy

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.

Other Names:

PIPAC

Outcome Measures

Primary Outcome Measures

Objective tumor response according to RECIST v 1.1 after second PIPAC [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 in CT scan performed 1 week after second PIPAC procedure

Secondary Outcome Measures

Objective tumor response according to RECIST v 1.1 [Day 7 after third PIPAC procedure (an average of 15 weeks after start of the study)]
Objective tumor response according to RECIST v 1.1 in CT scan performed 1 week after third PIPAC procedure
Compliance to treatment [Through study completion, an average of 28 months]
Proportion of patients able to receive all anticipated treatment (3 PIPACs and 6 cycles of FOLFOX)
Postoperative complication assessed by Clavien-Dindo score [Through study completion, an average of 28 months]
The number of patients with postoperative complications, defined and graded according to Clavien-Dindo classification
Peritoneal carcinomatosis index and histological regression according to peritoneal regression grading score (PRGS). [Through study completion, an average of 28 months]
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.
Ascites volume [Through study completion, an average of 28 months]
The volume of ascites recorded at every PIPAC procedure.
Tumor markers [Through study completion, an average of 28 months]
Ca19-9, carcinoembryonic antigen (CEA), Ca72-4 plasma levels measured at different time points.
Quality of life by EORTC questionnaires [Through study completion, an average of 28 months]
Quality of life by EORTC questionnaires measured at different time points.
Overall survival [From treatment start to death, assessed up to 24 months]
Time from start of the treatment to death
Progression-free survival [From treatment start to death, assessed up to 24 months]
Time from start of the treatment to progression of the disease
Adverse events of chemotherapy drugs [Through study completion, an average of 28 months]
The number of patients with toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0 during the study period

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically verified gastric adenocarcinoma (HER2 negative) with peritoneal carcinomatosis;
Age≥18;
ECOG≤1;
Patient willing to participate;
Patient is the candidate for 1st line FOLFOX palliative systemic chemotherapy.