PIPAC in Multimodal Therapy for Patients with Oligometastatic Peritoneal Gastric Cancer

NCT05303714 | Recruiting Phase 3

• 1 other identifier: PIPAC_VEROne
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

Peritoneal Carcinomatosis is the most frequent site of metastases observed in patients with gastric cancer. Current standard treatment for these patients is palliative systemic chemotherapy, but the prognosis is very poor. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) resulted in long-term benefits in selected patients with limited peritoneal involvement. Indeed, among patients with Peritoneal Carcinomatosis, a distinctive subset is oligometastatic disease which is characterized by low metastatic burden. PIPAC is a recent technique of intraperitoneal chemotherapy that can be used in combination with systemic chemotherapy with promising results for patients with PM from gastric cancer. The role of PIPAC in multimodal treatment path for oligometastatic gastric cancer should be investigated in clinical trials. PIPAC VER-One is a prospective, randomized, multicenter phase III clinical trial with two arms that aims to evaluate the effectiveness of the use of PIPAC in combination with systemic chemotherapy in patients with Gastric Cancer and synchronous positive peritoneal cytology and/or limited peritoneal metastases (PCI ≤ 6). Patients will be randomized into two arms: arm A (control) treated with the current standard that is systemic chemotherapy only and Arm B (experimental) treated with a bidirectional scheme including PIPAC and systemic chemotherapy (1 PIPAC every 2 systemic chemotherapy cycles). Primary endpoint is the Secondary Resectability Rate. Secondary endpoints are: Overall Survival, Progression Free Survival, Disease Free Survival, histological response assessed both on primary tumor and peritoneal lesions, Quality of Life, complication rate (CTCAE v5), incremental cost-effectiveness ratios (ICER).

Conditions

Oligometastatic Gastric Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Secondary Resectability Rate (percent)

  The rate of patients of the two arms that get radical intent surgery (cytoreductive surgery and HIPEC)

  Three and a half years

Secondary Outcomes (7)

• OS

  Three and a half years

• PFS

  Three and a half years

• DRS

  Three and a half years

• PRGS

  Three and a half years

• TRG

  Three and a half years

Study Arms (2)

Arm A (FOLFOX)

ACTIVE COMPARATOR

Patients randomized in the Arm A will undergo to 6 courses of systemic chemotherapy according to FOLFOX regimen, after these six courses of chemotherapy, radiologic restaging (CT scan) as well as a second staging laparoscopy will be performed. If a Progression Disease will be detected, the patient will end the trial and will undergo to II line chemotherapy regimen. If a stable disease or a partial response will be documented, after a multidisciplinary discussion, patient will undergo to either further 6 courses of chemotherapy or to cytoreductive surgery plus HIPEC.

Combination Product: FOLFOX and PIPAC

Arm B (FOLFOX and PIPAC)

EXPERIMENTAL

Patients randomized in the ARM B will undergo to 6 courses of systemic chemotherapy (FOLFOX regimen) plus PIPAC every two cycles of chemo (Fig.1). At least seven days should last between each PIPAC and the next chemotherapy course, and at least 14 days should last between the chemotherapy course and the next PIPAC. After six courses of chemotherapy and 3 PIPACs procedure, a radiologic restaging (CT scan) as well as a laparoscopic reassessment will be performed. If a Progression Disease will be detected, the patient will end the trial and will undergo to II line chemotherapy regimen. If a stable disease or a partial response will be documented, patient will be treated with cytoreductive surgery plus HIPEC.

Combination Product: FOLFOX and PIPAC

Interventions

FOLFOX and PIPAC COMBINATION_PRODUCT

A minilaparotomy is performed in the midline. A 5 mm balloon trocar is inserted under "finger protection" in the right side and the fascia of the minilaparotomy is closed. The abdomen is insufflated with CO2 and a second 10-12mm trocar is introduced under videoscope control in upper left side. Ascites volume is documented and removed sending a sample for cytological examination, an accurate exploratory laparoscopy is performed, possibly placing an additional 5 or 10-12 mmHg trocar, the Peritoneal Cancer Index is calculated. Multiple biopsies are performed in different abdominal quadrants. A nebulizer CAPNOPEN© is inserted into the upper left side trocar and fixed with a 45° angle. The drugs (Cisplatin 10.5 mg/m2 body surface in 150 mL; Doxorubicin 2.1 mg/m2 body surface in 50 mL) are then injected through remote control with a flow rate of 0.7 mL/sec with a pressure of 200 psi. After an aerosol exposure phase of 30min, the aerosol is evacuated via a closed waste system.

Arm A (FOLFOX); Arm B (FOLFOX and PIPAC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary resectable gastric cancer with positive peritoneal cytology and/or low burden peritoneal metastases (PCI ≤6) confirmed by laparoscopy
• Signature of written informed consent
• ECOG PS 0-1

You may not qualify if:

• Extraperitoneal metastases
• PCI \>6
• Gastro-esophageal junction tumor of esophageal relevance (Siewert I-II)
• Previous allergic reactions to cisplatin or doxorubicin
• Hemorrhagic or occlusive manifestation of the primary tumor with palliative surgery needed
• ASA IV
• Positivity for EBV, MSI and HER2 on diagnostic biopsies
• Pregnancy and breastfeeding
• Contraindication to any drug contained in the chemotherapy regimen
• Hepatic impairment (AST/ALT\> 3 times normal values, ALT\>3 times normal values, Bilirubin\>1.5 normal values)
• Ischemic/hemorrhagic stroke in the last 6 months
• Acute myocardial infarction in the last 6 months
• Moderate/severe heart failure (NYHA III-IV)
• Leukopenia\< 2,000/μl
• Thrombocytopenia \< 100,000/μl

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Integrata Verona: lead

Study Sites (1)

AOUI Verona

Verona, 37126, Italy

RECRUITING

Related Links

• University of Verona

MeSH Terms

Interventions

Folfox protocol

Study Officials

• Francesco Casella

  General and Upper GI Surgery, University of Verona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Casella

CONTACT

+390458123123; francesco.casella@aovr.veneto.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Francesco Casella MD, Principal Investigator

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 31, 2022
• Study Start: March 31, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2028
• Last Updated: February 21, 2025

Record last verified: 2024-08

Locations

IT (1)