Study of Efficacy and Safety of Laparoscopic Intra-abdominal Chemotherapy (PIPAC) Performed in Patients With Peritoneal Carcinomatosis From Colorectal, Ovarian, Gastric Cancer and Primary Peritoneal Tumors

Study Overview
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Brief Summary
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Single center, open label, phase I-II, non-randomized, two-cohort, repeated single dose study to explore the feasibility, efficacy, safety, and Overall Response Rate (ORR) of oxaliplatin, or cisplatin and doxorubicin when given as a pressurized intraperitoneal chemotherapy (PIPAC) to patients (men and women) with peritoneal carcinomatosis from ovarian, gastric and colorectal cancers and in primary cancers of peritoneum.

Official Title
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Feasibility, Efficacy and Safety of Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) With Oxaliplatin, Cisplatin and Doxorubicin in Patients With Peritoneal Carcinomatosis From Colorectal, Ovarian, Gastric Cancers and Primary Tumors of the Peritoneum: An Open-label, Two-arms, Phase I-II Clinical Trial. PI-CaP

Conditions
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Peritoneal Carcinomatosis

Intervention / Treatment
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* Drug: Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) fixed repeated dose
* Drug: Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) increasing single dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical and pathological confirmation of peritoneal carcinomatosis from gastric, colorectal and ovarian cancers or primary peritoneal tumors. Patients aged between 18 and 78 years. Performance status sec. ECOG ≤ 2 Disease progression/relapse after at least one line of previous i.v. standard chemotherapy in gastric cancer and primary peritoneal tumors and two lines in colorectal and ovarian cancers. Patients with peritoneal carcinomatosis from ovarian, gastric and colorectal cancers and primary peritoneal cancers not eligible to cytoreductive surgery +/- HIPEC. Blood and electrolyte counts, liver, renal and cardiopulmonary function parameters within 10% of the normal range. Written informed consent. Tumor mass present on CT-scan in order to allow tumor response assessment with RECIST-criteria. Exclusion Criteria: Extra-abdominal metastatic disease, with the exception of isolated pleural carcinomatosis. Bowel obstruction. Severe renal impairment, myelosuppression, severe hepatic impairment, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias. Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system. Creatinine clearance < 60 ml /min. Pregnancy. Previous treatment reaching the maximum cumulative dose of doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines and anthracenediones. Known allergy to cisplatin or other platinum-containing compounds or to doxorubicin. Patients of both sexes who do not conduct complete abstinence from heterosexual relationships or agree to use an effective clinically acceptable method (with failure rate <1%) during the study and the following 6 months after the last treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 78 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two parallel cohorts according to patients characteristics Patient with indication for systemic standard chemotherapy will be accrued in Cohort A (for a Phase II repeated single dose PIPAC). Patient with no indication for sistemic standard chemotheralpy will be accrued in Cohort B ( for a Phase, single ascending dose PIPAC)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort A<br>Cohort A: For patients that have indication for systemic therapy with standard chemotherapy. This cohort has a phase II design; the Objective Response Rate (ORR) will be evaluated according to the RECIST criteria (version 1.1) after 2 and 3 cycles of PIPAC with Cisplatin (7.5 mg/m²) + Doxorubicin (1.5 mg/m2 ) or Oxaliplatin (92 mg/m2) according to the primary cancer, in association with standard systemic chemotherapy. | Drug: Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) fixed repeated dose<br>* An open access with a midline 5-6 cm incision is performed and a single-port platform is positioned. A 12 mm Hg CO2 pneumoperitoneum is inflated. PC extent is evaluated according to Peritoneal Cancer Index (PCI) and peritoneal biopsies are taken. A nebulizer is connected to an intravenous high-pressure injector and inserted into the peritoneal cavity; the tightness of the abdomen has to be documented with a CO2 zero-flow. The laparoscopic camera and the nebulizer are maintained in position by a self-retaining retractor (Thompson). A pressurized aerosol containing drugs is delivered. Standard dosage of drugs for each PIPAC: Cisplatin (7.5 mg/m²) + Doxorubicin (1.5 mg/m²) or Oxaliplatin (92 mg/m²) The capnoperitoneum is then maintained for 30 minutes at 37°C. At the end, the aerosol is exsufflated through two sequential micro-particle filters into the air-waste system of the hospital.<br>* Other names: Cisplatin + Doxorubicin in ovarian, gastric cancer and in primary peritoneal tumors; or Oxaliplatin in colorectal cancer;|
| Experimental: cohort B<br>Cohort B: For patients that have not indication for systemic therapy with standard chemotherapy. This cohort has a phase I design; with a dose-escalation design the maximum tolerated doses and recommended doses of Cisplatin + Doxorubicin and Oxaliplatin (according to the pathology) administered through PIPAC in patients with peritoneal carcinomatosis will be evaluated. | Drug: Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) increasing single dose<br>* An open access with a midline 5-6 cm incision is performed and a single-port platform is positioned. A 12 mm Hg CO2 pneumoperitoneum is inflated. PC extent is evaluated according to Peritoneal Cancer Index (PCI) and peritoneal biopsies are taken. A nebulizer is connected to an intravenous high-pressure injector and inserted into the peritoneal cavity; the tightness of the abdomen has to be documented with a CO2 zero-flow. The laparoscopic camera and the nebulizer are maintained in position by a self-retaining retractor (Thompson). A pressurized aerosol containing drugs is delivered. Escalating dosage of drugs for PIPAC: Cisplatin + Doxorubicin (from 15 mg/m² + 3 mg/m² to 100 mg/m² + 30 mg/m²) or Oxaliplatin (from 92 mg/m² to 300mg/m²).The capnoperitoneum is then maintained for 30 minutes at 37°C. At the end, the aerosol is exsufflated through two sequential micro-particle filters.<br>* Other names: Cisplatin + Doxorubicin in ovarian, gastric cancer and in primary peritoneal tumors; or Oxaliplatin in colorectal cancer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) according to RECIST criteria (version 1.1) after 2 and 3 cycles of PIPAC. |  | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The overall survival (OS) |  | 30 months | 
| The degree of histological regression assessed by pathological review |  | 18 weeks | 
| The median time to progression (TTP) according to RECIST criteria (version 1.1) after two or three cycles of PIPAC |  | 30 months | 
| Measurement of clinical tumor response to therapy using FDG- Positron Emission Tomography (PET) according to PERCIST criteria (version 1.0). |  | 22 weeks | 
| The Peritoneal Carcinomatosis Index (PCI) before and after therapy |  | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pressurized Intra Peritoneal Air-flow Chemotherapy (PIPAC), Chemotherapy, Peritoneal Carcinomatosis