Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Applied to Platinum-Resistant Recurrence of Ovarian Tumor

Study Overview
=================
Brief Summary
-----------------
Patients with first recurrent resistance ovarian cancer and disease progression with peritoneal carcinomatosis will undergo PIPAC procedure. The primary end point is to determine the clinical benefit rate (CBR) of a pressurized intraperitoneal aerosol chemotherapy with a combination of cisplatin and doxorubicin.

Detailed Description
-----------------
This study aims to investigate the therapeutic efficacy of PIPAC using cisplatin and doxorubicin in women with first recurrent resistance ovarian cancer and disease progression with peritoneal carcinomatosis. The primary objective of this study is to determine the Clinical Benefit Rate (CBR) according to RECIST/GCOG criteria after three cycles of PIPAC with PIPAC cisplatin and doxorubicin

Official Title
-----------------
Feasibility, Efficacy and Safety of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) With Cisplatin in Women With Recurrent Ovarian Cancer: an Open-label, Single-arm Phase I-II Clinical Trial

Conditions
-----------------
Ovarian Epithelial Cancer Recurrent, Platinum-resistant

Intervention / Treatment
-----------------
* Device: Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients affected by first or second platinum resistant epithelial ovarian tumor recurrence. ECOG-performance status ≤ 3. Adequate respiratory, hepatic, cardiac, kidney and bone marrow function (absolute neutrophil count > 1500 / mm3, platelets > 150 000/μl, creatinine clearance > 60 mL / min according to Cockroft formula). Patient-compliant and psychologically able to follow the trial procedures. Exclusion Criteria: Non-epithelial ovarian cancer or borderline ovarian tumor. Pregnancy or breastfeeding. Patients affected by major depressive disorder even in treatment or minor mood disorders. Patients with severe impairment of respiratory, hepatic or renal function. Patients with cardiac, neurological or metabolic uncontrolled pharmacologically disease Patients with bowel obstruction. Inadequate bone marrow, liver, kidney function. No clear-peritoneal disease at surgical exploration. Patients with ascites >2000 cc (CT-Scan) Patients who have already made third line chemotherapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PIPAC<br>PIPAC stands for Pressurized IntraPeritoneal Aerosol Chemotherapies. Enrolled patients will undergo to explorative laparoscopy as usual and PC index will be determined according to Fagotti score (PIV). Pathological response will be determined by serial peritoneal biopsies. Then a pressurized aerosol containing cisplatin followed by doxorubicin will be applied via a nebulizer. The PIPAC procedure can be repeated after 4-6 weeks until progression or limiting toxicity | Device: Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin<br>* After insufflation of a 12 mmHg of capnoperitoneum at 37 °C, two balloon trocars will be placed. Parietal biopsies will be taken and ascites (< 500cc) will be removed. A nebulizer will be connected to a high-pressure injector and will be inserted into the abdomen through a trocar. A pressurized aerosol containing cisplatin at a dose of 10.5 mg/m2 body surface in 150 ml NaCl 0.9 % followed by doxorubicin at a dose of 2.1 mg/m2 body surface in a 50 ml NaCl 0.9% solution will be applied via a nebulizer immediately. Then, the system will be kept in steady-state for 30 min (i.e.: application time).<br>* Other names: PIPAC;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate (CBR) according to RECIST/GCOG criteria after three cycles of PIPAC with PIPAC cisplatin and doxorubicin | Evaluation of target lesions will be done as follows: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase | 12-18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The median time to progression according to RECIST criteria after three cycles of PIPAC with cisplatin | From the last chemotherapy cycle to the first clinical-radiological signs of disease relapse | 1 Year | 
| Fagotti score, as assessed by laparoscopy |  | 1 Year | 
| The degree of histological regression assessed by pathological review of repeated peritoneal biopsies |  | 1 Year | 
| The proportion of women with a reduction of serum CA-125 of at least 50% after PIPAC |  | 1 Year | 
| Evaluation of the Quality Of Life (QOL) on the basis of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires | Quality of life will be assess using the EORTC quality of life questionnaire core-36 (QLQC-30) and the ovarian cancer-specific quality of life questionnaire (QLQ-Ov28).These will be complete before and after the first, second, and third PIPAC applications | 1 year |