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PIPAC and FOLFOX for Gastric Cancer Peritoneal Cancer

Not Applicable
Recruiting
Conditions
Peritoneal Carcinomatosis
Gastric Cancer
Interventions
Registration Number
NCT05644249
Lead Sponsor
Vilnius University
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
37
Inclusion Criteria
  1. Histologically verified gastric adenocarcinoma (HER2 negative) with peritoneal carcinomatosis;
  2. Age≥18;
  3. ECOG≤1;
  4. Patient willing to participate;
  5. Patient is the candidate for 1st line FOLFOX palliative systemic chemotherapy.
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Exclusion Criteria
  1. Extra-abdominal metastases;
  2. Siewert I type gastroesophageal junction cancer;
  3. Mechanical bowel obstruction;
  4. Allergy to study drugs;
  5. History of previous intraperitoneal chemotherapy;
  6. Pregnancy of refusal for birth-control at least 6 months post-study treatment
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Experimental treatmentCombined Doxorubicin and Cisplatin Pressurized IntraPeritoneal Aerosol Chemotherapy With Systemic FOLFOX chemotherapyEach 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.
Primary Outcome Measures
NameTimeMethod
Objective tumor response according to RECIST v 1.1 after second PIPACDay 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
NameTimeMethod
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 volumeThrough study completion, an average of 28 months

The volume of ascites recorded at every PIPAC procedure.

Overall survivalFrom treatment start to death, assessed up to 24 months

Time from start of the treatment to death

Postoperative complication assessed by Clavien-Dindo scoreThrough study completion, an average of 28 months

The number of patients with postoperative complications, defined and graded according to Clavien-Dindo classification

Progression-free survivalFrom treatment start to death, assessed up to 24 months

Time from start of the treatment to progression of the disease

Compliance to treatmentThrough study completion, an average of 28 months

Proportion of patients able to receive all anticipated treatment (3 PIPACs and 6 cycles of FOLFOX)

Adverse events of chemotherapy drugsThrough 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

Tumor markersThrough study completion, an average of 28 months

Ca19-9, carcinoembryonic antigen (CEA), Ca72-4 plasma levels measured at different time points.

Objective tumor response according to RECIST v 1.1Day 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

Quality of life by EORTC questionnairesThrough study completion, an average of 28 months

Quality of life by EORTC questionnaires measured at different time points.

Trial Locations

Locations (2)

Nationa Cancer Institute

🇱🇹

Vilnius, Vilniaus, Lithuania

Vilnius University hospital Santaros Klinikos

🇱🇹

Vilnius, Vilniaus, Lithuania

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