Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as a Component of Combined Treatment in Patients With Advanced Epithelial Ovarian Cancer and Peritoneal Carcinomatosis: A Randomized Phase II Trial (PrimPIPAC)
Phase: PHASE2
Conditions: Advanced Epithelial Ovarian Cancer, Peritoneal Carcinomatosis
Sponsor: Moscow Regional Oncological Dispensary

 
 
 
 
 
 
Pressurized Intraperitoneal Aerosol Chemotherapy 
(PIPAC) as a Component of Combined Treatment in Patients with 
Advanced Epithelial Ovarian Cancer and Peritoneal 
Carcinomatosis: A Randomized Phase II Trial (PrimPIPAC) 
 
Phase: II 
Study Design: Prospective, randomized, open-label, controlled trial 
Sponsor: Peoples' Friendship University of Russia (RUDN University), in collaboration with P.A. 
Hertzen Moscow Oncology Research Institute and Moscow Regional Oncological Dispensary, 
Russian Federation 
IND Status: To be determined (cisplatin approved agent; PIPAC delivery investigational use) 
Principal Investigator: 
Alexey S. Dzasokhov, MD, PhD, Head of the Department of Gynecologic Oncology No. 5, 
Moscow Regional Oncological Dispensary, Balashiha, Russian Federation, 
Email: dzasokhov.pipac@gmail.com, dzasokhov-pipac@mail.ru 
NCT Number: NCT ID not yet assigned 
Document Date: March 31th 2026 
 
 

2. STUDY SCHEMA 
Population: Women aged 18-75 years with newly diagnosed FIGO IIIB-IIIC ovarian cancer, 
visually detectable peritoneal carcinomatosis. 
Randomization (controlled, intraoperative): 
 The source protocol defines the trial as randomized and controlled; a formal allocation ratio and 
stratification scheme are not specified. 
Arm A - Experimental: 
TC systemic chemotherapy plus cisplatin-based PIPAC x 3 procedures: 
 At initial diagnostic laparoscopy/laparotomy (PIPAC-1) 
 During induction treatment before interval cytoreduction (PIPAC-2) 
 Immediately after interval cytoreductive surgery (PIPAC-3) 
Arm B - Comparison: 
Standard combined treatment with one PIPAC procedure performed simultaneously with interval 
cytoreductive surgery; this corresponds in timing to PIPAC-3 in the experimental arm. 
Third study branch: 
Patients from either arm in whom complete cytoreduction is not achieved receive postoperative TC 
courses 4 and 5, one additional PIPAC procedure, and then systemic chemotherapy course 6. 
 
3. OBJECTIVES 
3.1 Primary Objective 
To improve the efficacy of combined treatment in ovarian cancer with peritoneal carcinomatosis by 
incorporating repeated PIPAC into the drug-therapy component of standard management.  
3.2 Secondary Objectives 
 Evaluate induction-treatment efficacy by PCI dynamics, ascites and morphological response. 
 Assess toxicity and tolerability of platinum-based PIPAC combined with systemic 
chemotherapy. 
 Evaluate progression-free survival, overall survival, recurrence rate, time to recurrence, and 
patterns of progression. 
3.3 Exploratory Objectives 
 Standardize the integration of PIPAC with neoadjuvant and postoperative systemic therapy, 
including indications and contraindications. 
 Assess whether additional postoperative PIPAC may improve outcomes after incomplete 
cytoreduction. 
 
 

4. BACKGROUND AND RATIONALE 
Peritoneal carcinomatosis is one of the principal manifestations of advanced ovarian cancer and a 
major cause of treatment failure. Although combined systemic therapy and surgery remain 
standard, prognosis worsens substantially when the peritoneal tumor burden is high and optimal 
cytoreduction is difficult to achieve. 
In patients with extensive peritoneal dissemination, aggressive surgery alone may be technically 
infeasible or associated with significant morbidity. Locoregional intraperitoneal treatment therefore 
remains an important therapeutic objective. 
PIPAC enables pressurized aerosol delivery of chemotherapy into the peritoneal cavity and is 
intended to improve tissue distribution while limiting systemic exposure. The protocol therefore 
evaluates repeated cisplatin-based PIPAC as an additional component of first-line combined 
treatment in ovarian cancer with peritoneal carcinomatosis. 
 
5. ELIGIBILITY CRITERIA 
5.1 Inclusion Criteria 
 Female, age 18-75 years. 
 Histologically verified ovarian cancer with peritoneal carcinomatosis. 
 FIGO stage IIIB or IIIC. 
 visually detectable peritoneal carcinomatosis. 
 Peritoneal metastatic involvement documented preoperatively by ultrasound, CT, MRI, PET-
CT, or equivalent imaging. 
 Ability to comply with protocol procedures and provide written informed consent. 
5.2 Exclusion Criteria 
 Age > 75 years; ECOG 3-4; cachexia with BMI <= 16. 
 Severe concomitant disease in exacerbation or decompensation. 
 Extra-abdominal metastases, including metastatic pleuritis. 
 Mucinous ovarian carcinoma or another active malignant neoplasm, except malignancies in 
clinical remission for more than 2 years. 
 Pronounced adhesive disease of the abdominal cavity. 
 Pregnancy or breastfeeding. 
 Positive BRCA1 or BRCA2 status. 
 Any condition precluding safe PIPAC or protocol execution, including hollow-organ perforation, 
gastrointestinal resection with anastomosis, or repair of a hollow-viscus defect. 
 Refusal of treatment at any study stage. 
 
 

6. TREATMENT PLAN 
6.1 Surgery 
 Diagnostic laparoscopy or, when laparoscopy is not feasible, diagnostic laparotomy. 
 Ascites volume, visceral and parietal peritoneal involvement, and the PCI according to 
Sugarbaker are documented. 
 Peritoneal, ovarian, and omental biopsies are obtained; the primary tumor is not removed 
during the diagnostic stage. 
 First PIPAC is performed immediately after pathologic verification of carcinomatosis. 
6.2 Systemic Chemotherapy 
 Systemic chemotherapy is administered according to the TC regimen at 3-week intervals. 
 When PIPAC is combined with cytoreductive surgery, postoperative systemic chemotherapy 
starts 7-21 days after surgery. 
 When PIPAC is performed as a standalone procedure, systemic chemotherapy starts 1-10 
days after intraperitoneal treatment. 
6.3 PIPAC Procedure 
Performed laparoscopically under general anesthesia. 
Drug: cisplatin 30 mg/m² diluted in 180 mL normal saline 
Administration: 
 Capnoperitoneum established with carbon dioxide at a target pressure of 12-14 mmHg. 
 Flow settings depend on nozzle size: No. 150, 0.3-0.4 mL/s; No. 200, 0.7-0.8 mL/s. 
 Nebulizer selection depends on patient height and body-mass index; tense ascites is 
evacuated before treatment. 
 The aerosol flow is directed toward the largest free intraperitoneal space and away from hollow 
viscera, ligated vessels, and tumor beds. 
 Exposure time is maintained for exactly 30 minutes. 
 The abdomen is decompressed without aspirating the cytostatic solution, and no drain is left in 
place. 
6.4 Interval Cytoreductive Surgery 
 Performed after the second PIPAC session and the third course of neoadjuvant chemotherapy. 
 The planned operative volume includes total hysterectomy with adnexa, omentectomy, 
peritonectomy, or multifocal peritoneal biopsy when indicated. 
 The surgical aim is maximal cytoreduction; residual disease is categorized as complete or 
suboptimal cytoreduction. 
 Before abdominal-wall closure, two trocars are positioned and a further PIPAC session is 
performed in the same operative setting. 
6.5 Third Study Branch 
 Patients from either arm in whom complete cytoreduction is not achieved receive postoperative 
TC chemotherapy courses 4 and 5, an additional PIPAC procedure, and then chemotherapy 
course 6. 
 
 

7. STUDY ASSESSMENTS 
7.1 Baseline / Screening 
 Eligibility assessment, physical examination, vital signs, anthropometry, ECOG, gynecologic 
examination. 
 CBC, urinalysis, biochemistry, coagulation studies, infection screening, venous Doppler, 
echocardiography, ECG, and thromboembolic-risk assessment. 
 Tumor markers including CA-125, HE4, and CA 19-9; BRCA status; histology; ascites puncture 
if indicated. 
 Imaging with CT, MRI, PET-CT, ultrasound, or clinically equivalent modalities. 
7.2 During Treatment 
 At each operative stage: ascites-volume assessment, PCI reassessment, biopsy sampling, 
histology, and adverse-event recording. 
 At each systemic-chemotherapy visit: clinical examination, laboratory testing, dose calculation, 
premedication, and safety assessment. 
 Histologic response is assessed after repeat procedures using treatment-regression evaluation 
specified by the protocol. 
7.3 Follow-up 
 Follow-up visits are performed every 3 months during the first 2 years after treatment. 
 Assessments include physical examination, tumor markers when initially elevated, ultrasound 
of abdomen and pelvis, CT chest, MRI pelvis or CT abdomen as indicated, and ascites 
puncture when needed. 
 Quality of life is evaluated with EORTC questionnaires during follow-up. 
 
8. ENDPOINT DEFINITIONS 
8.1 Primary Endpoint Domain 
Primary endpoint – is complete surgical cytoreduction (CRS R0). 
8.2 Response Criteria 
 PCI complete response - PCI < 3 together with negative results on at least three biopsy 
samplings. 
 PCI partial response - reduction of PCI by at least 4 points. 
 PCI progression - increase of PCI by at least 4 points or appearance of one or more new 
lesions. 
 PCI stable disease - response pattern meeting neither partial-response nor progression criteria. 
Clinical response is evaluated according to RECIST 1.1; morphologic response is assessed 
according to protocol-defined TRG criteria. 
 
 

8.3 Secondary Endpoints 
 Overall survival, progression-free survival, median survival, recurrence rate, and time to 
progression. 
 Rate of ascites accumulation and proportion of patients with at least 50% reduction in tumor-
marker levels. 
 Frequency and severity of adverse events, wound-healing time, intestinal paresis, and 
laboratory abnormalities. 
 
9. STATISTICAL CONSIDERATIONS 
9.1 Planned Sample Size 
At least 160 patients will be enrolled. Accrual is planned for 5 years from enrollment of the first 
randomized patient. 
9.2 Analysis Framework 
The source protocol does not define a separate formal power calculation or detailed ITT/mITT/per-
protocol populations. 
 All enrolled and treated patients will contribute to the protocol evaluations. 
 Analyses are planned according to study arm and extent of cytoreduction, as appropriate. 
9.3 Statistical Methods 
 Quantitative variables will be summarized by mean, standard deviation, and standard error of 
the mean. 
 Nominal and ordinal variables will be summarized as frequencies and percentages. 
 Safety endpoints will be reported descriptively and include all adverse events, events leading to 
withdrawal, and events considered treatment-related. 
 
10. SAFETY MONITORING 
 All adverse events occurring after signature of informed consent must be identified and 
documented. 
 For each adverse event, the investigator records onset date, duration, intensity, treatment 
required, outcome, and action taken with study treatment. 
 Serious adverse events are defined as events leading to death, an immediately life-threatening 
condition, persistent or significant disability, hospitalization or prolongation of hospitalization, or 
another medically significant condition. 
 
 

 During PIPAC, staff exposure to cytostatics must be minimized by use of disposable linen, 
double gloves, masks, protective eyewear, and sealed disposal containers. 
 Pregnant and breastfeeding staff members must not work in the operating room during the 
procedure. 
 
11. DATA MANAGEMENT 
 Written informed-consent forms, discharge summaries, source medical records, and protocol-
specific case documentation are retained by the investigator. 
 CRF data are grouped in an Excel database; the case-report forms, source statistical 
processing, and supporting materials remain available for verification. 
 CRFs are signed by the investigator and the head of department; patients are identified in study 
documents by coded identifiers rather than full names. 
 All study documentation, including source data and protocol files, must remain accessible for 
direct review by monitors, auditors, ethics committees, and regulatory authorities. 
 
12. ETHICAL CONSIDERATIONS 
 The study is conducted in accordance with the Declaration of Helsinki, OST 42-511-99 on 
quality clinical trials, and applicable Russian regulatory requirements. 
 Ethics Committee approval is required before study initiation and for any material protocol 
amendment. 
 Written informed consent is mandatory before any study-specific procedure is performed. 
 Patient rights, safety, well-being, and confidentiality take precedence over the interests of 
science and society. 
 
13. CORRELATIVE STUDIES (OPTIONAL) 
 BRCA status determination at screening; patients with positive BRCA status are excluded 
according to the source protocol. 
 TRG-based histologic assessment of serial peritoneal and omental specimens. 
 Serial tumor-marker evaluation and quality-of-life assessment during follow-up. 
 
 

14. STUDY DURATION 
Accrual period: up to 5 years from enrollment of the first randomized patient. 
Follow-up: every 3 months during the first 2 years after completion of therapy. 
Total duration: approximately 5 years of accrual plus protocol-defined follow-up. 
APPENDICES (on request) 
 Appendix A: Visit Schedule and Assessment Matrix 
 Appendix B: PIPAC Technical Procedure 
 Appendix C: TRG / Morphologic Response Assessment 
 Appendix D: RECIST 1.1 and PCI Response Definitions 
 Appendix E: Toxicity and Safety Reporting 
 Appendix F: Informed Consent Template