PIPAC and FOLFOX for Gastric Cancer Peritoneal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Gastric Cancer, Peritoneal Carcinomatosis

Intervention / Treatment
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* Drug: Combined Doxorubicin and Cisplatin Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic FOLFOX chemotherapy


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Extra-abdominal metastases; Siewert I type gastroesophageal junction cancer; Mechanical bowel obstruction; Allergy to study drugs; History of previous intraperitoneal chemotherapy; Pregnancy of refusal for birth-control at least 6 months post-study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental treatment<br>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<br>* 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.<br>* Other names: PIPAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Day 7 after second PIPAC procedure (an average of 8 weeks after start of the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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) | 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 | 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. | Through study completion, an average of 28 months | 
| Ascites volume | The volume of ascites recorded at every PIPAC procedure. | Through study completion, an average of 28 months | 
| Tumor markers | Ca19-9, carcinoembryonic antigen (CEA), Ca72-4 plasma levels measured at different time points. | 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. | Through study completion, an average of 28 months | 
| Overall survival | Time from start of the treatment to death | From treatment start to death, assessed up to 24 months | 
| Progression-free survival | Time from start of the treatment to progression of the disease | 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 | Through study completion, an average of 28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric cancer, Peritoneal carcinomatosis, PIPAC, FOLFOX, Bidirectional