Intensification Treatment of Ovarian Cancer by PIPAC (PrimPIPAC)

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)

The goal of this clinical trial is to learn whether repeated cisplatin-based PIPAC added to standard TC chemotherapy can improve outcomes in women aged 18-75 years with newly diagnosed FIGO IIIB-IIIC epithelial ovarian cancer and visually detectable peritoneal carcinomatosis. The main questions are whether repeated PIPAC increases the rate of complete surgical cytoreduction (CRS R0) and whether it improves disease control, survival outcomes, and safety compared with standard combined treatment including a single PIPAC procedure. Participants will undergo screening, intraoperative randomization, systemic chemotherapy, PIPAC procedures according to study arm, interval cytoreductive surgery, protocol-specified postoperative treatment if needed, and regular follow-up assessments.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Carcinomatosis; Advanced Epithelial Ovarian Cancer
• Intervention / Treatment: Procedure: PIPAC

Detailed Description

Advanced epithelial ovarian cancer is frequently accompanied by peritoneal carcinomatosis, which is a major determinant of treatment failure and poor long-term prognosis. Although systemic platinum-taxane chemotherapy and cytoreductive surgery remain the foundation of first-line management, outcomes are substantially worse when intraperitoneal tumor burden is high and complete cytoreduction is difficult to achieve. In this setting, additional locoregional treatment strategies may help improve intraperitoneal disease control while preserving the feasibility of multimodal therapy. The present study evaluates pressurized intraperitoneal aerosol chemotherapy (PIPAC) as an investigational component of combined first-line treatment for advanced ovarian cancer with peritoneal dissemination.

PIPAC delivers intraperitoneal chemotherapy as a pressurized aerosol during laparoscopy and is intended to enhance spatial distribution and tissue penetration of the drug while limiting systemic exposure. In this protocol, cisplatin-based PIPAC is integrated into the treatment pathway at predefined operative stages together with standard TC systemic chemotherapy and interval cytoreductive surgery. The study is designed as a prospective, randomized, open-label, controlled phase II trial comparing a strategy of repeated PIPAC incorporated across the course of induction and surgical treatment with a comparison strategy in which PIPAC is delivered only once during interval cytoreductive surgery. The protocol also includes further protocol-directed treatment for patients in whom complete cytoreduction is not achieved.

At the diagnostic operative stage, disease extent is documented using intra-abdominal assessment including ascites evaluation, mapping of visceral and parietal peritoneal involvement, and calculation of the Peritoneal Cancer Index. Peritoneal, ovarian, and omental tissue samples are obtained for histologic verification and subsequent treatment-response assessment. PIPAC is administered laparoscopically under general anesthesia using cisplatin diluted in normal saline, delivered into a carbon dioxide capnoperitoneum under controlled pressure and flow conditions with a fixed exposure time. Interval cytoreductive surgery is planned after induction treatment, and when indicated, an additional intraoperative PIPAC procedure is performed before abdominal-wall closure.

Throughout the study, participants undergo protocol-defined clinical, laboratory, imaging, and pathologic evaluations during treatment and follow-up. Serial reassessment of intraperitoneal disease, biopsy-based morphologic evaluation, tumor-marker monitoring, and adverse-event documentation are used to characterize treatment activity and tolerability over time. Follow-up continues at regular intervals after completion of therapy and includes oncologic surveillance and quality-of-life assessment. Safety oversight includes detailed documentation of adverse events and specific operating-room precautions intended to minimize occupational exposure during aerosolized intraperitoneal chemotherapy procedures. Study conduct, documentation, and confidentiality are governed by protocol-defined data-management procedures and ethical requirements, including written informed consent and ethics committee approval before study initiation and for major protocol amendments.

This trial is intended not only to evaluate the clinical contribution of repeated PIPAC in the first-line setting, but also to refine a practical treatment sequence for combining intraperitoneal aerosol chemotherapy with neoadjuvant systemic therapy, interval surgery, and postoperative management in patients with advanced ovarian cancer and peritoneal carcinomatosis.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alexey S. Dzasokhov, MD, PhD; Phone Number: +79295596135; Email: dzasokhov-pipac@mail.ru

Study Locations

• Russia
  • Balashikha, Russia, 14390
    • Recruiting
    • Moscow Regional Oncological Dispensary
    • Contact: Alexey S. Dzasokhov, MD, PhD; Phone Number: +79295596135; Email: dzasokhov-pipac@mail.ru
    • Contact: Alexey S. Dzasokhov, MD, PhD; Phone Number: +79295596135; Email: dzasokhov.pipac@gmail.com
    • Principal Investigator: Alexey S. Dzasokhov, MD, PhD
    • Sub-Investigator: Sergei O. Gunyakov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group with 3 PIPAC procedures; Participants undergo a multimodal treatment sequence consisting of diagnostic laparoscopy with multifocal peritoneal biopsy, repeated PIPAC procedures, systemic TC chemotherapy, and cytoreductive surgery. At Visit 1, participants receive diagnostic laparoscopy, multifocal peritoneal biopsy, the first PIPAC session, and the first cycle of intravenous TC chemotherapy. Visit 2 includes the second cycle of intravenous TC chemotherapy. At Visit 3, participants undergo the second PIPAC session and receive the third cycle of TC chemotherapy. At Visit 4, participants undergo cytoreductive surgery (CRS), the third PIPAC session, and the fourth cycle of intravenous TC chemotherapy. In patients achieving complete cytoreduction (CRS R0), treatment is followed by Visits 5 and 6, corresponding to the fifth and sixth cycles of TC chemotherapy.	Procedure: PIPAC; 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.
Active Comparator: Control group with 1 PIPAC procedure; Participants undergo a multimodal treatment sequence consisting of diagnostic laparoscopy with multifocal peritoneal biopsy, systemic TC chemotherapy, cytoreductive surgery, and a single PIPAC procedure. At Visit 1, participants undergo diagnostic laparoscopy, multifocal peritoneal biopsy, and receive the first cycle of intravenous TC chemotherapy. Visit 2 includes the second cycle of intravenous TC chemotherapy. At Visit 3, participants receive the third cycle of TC chemotherapy. At Visit 4, participants undergo cytoreductive surgery (CRS), a single PIPAC procedure, and the fourth cycle of intravenous TC chemotherapy. In patients achieving complete cytoreduction (CRS R0), treatment is continued with Visits 5 and 6, corresponding to the fifth and sixth cycles of TC chemotherapy.	Procedure: PIPAC; 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.
Active Comparator: Crossover group with additional PIPAC; Participants from either randomized arm who have incomplete cytoreduction (CRS R2) at Visit 4 enter a crossover treatment branch. After cytoreductive surgery, treatment is continued with postoperative TC chemotherapy. At Visit 5, participants receive the fifth cycle of intravenous TC chemotherapy. At Visit 6, participants undergo one additional PIPAC procedure followed by the sixth cycle of intravenous TC chemotherapy. This crossover branch is intended for participants in whom complete cytoreduction is not achieved.	Procedure: PIPAC; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete surgical cytoreduction (CRS R0)	The proportion of participants who achieve complete surgical cytoreduction (CRS R0) at interval cytoreductive surgery.	At interval cytoreductive surgery (Visit 4), approximately 9 to 12 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death from any cause.	From randomization through follow-up, assessed up to 2 years after completion of treatment
Progression-free survival	Time from randomization to radiologic, clinical, or pathologic disease progression or death from any cause, whichever occurs first.	From randomization through follow-up, assessed up to 2 years after completion of treatment
Recurrence rate	Proportion of participants with documented disease recurrence after completion of protocol treatment.	From completion of treatment through follow-up, assessed up to 2 years Recurrence rate is named among the secondary endpoints.
Time to progression	Time from randomization to first documented disease progression.	From randomization through follow-up, assessed up to 2 years after completion of treatment
Ascites response	Rate of ascites accumulation during treatment and follow-up, including change in ascites volume over time.	During treatment through follow-up, assessed up to 2 years after completion of treatment The protocol identifies rate of ascites accumulation as a secondary endpoint and also requires ascites-volume assessment at each operative stage.
Tumor marker response	Proportion of participants with at least a 50% reduction in tumor-marker levels from baseline.	During treatment and follow-up, assessed up to 2 years after completion of treatment The protocol specifies the proportion of patients with at least 50% reduction in tumor-marker levels as a secondary endpoint.
Frequency and severity of adverse events	Incidence, type, and severity of adverse events recorded after informed consent, including treatment-related adverse events and serious adverse events.	From informed consent through follow-up, assessed up to 2 years after completion of treatment
Intestinal paresis	Incidence of postoperative intestinal paresis during protocol treatment.	During treatment, assessed through completion of treatment Intestinal paresis is specifically listed among the secondary endpoints (assessed up to 6 months)
Laboratory abnormalities	Incidence and severity of clinically significant hematologic and biochemical laboratory abnormalities during protocol treatment.	During treatment and follow-up, assessed up to 2 years after completion of treatment Laboratory abnormalities are included in the secondary endpoint list, and laboratory testing is performed repeatedly during treatment and follow-up.
Wound-healing time	Time to postoperative wound healing after protocol-defined surgical procedures.	From the date of surgery to complete wound healing, assessed up to 30 days after each study-related surgical procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peritoneal Cancer Index (PCI) response	Change in Peritoneal Cancer Index from baseline, categorized according to protocol-defined response criteria: complete response, partial response, stable disease, or progression.	At baseline, before the second PIPAC procedure (approximately 6 weeks after randomization), and at interval cytoreductive surgery (approximately 9 to 12 weeks after randomization)
Morphologic response in peritoneal and omental biopsy specimens	Histologic treatment response assessed in serial biopsy specimens using protocol-defined treatment-regression criteria.	At baseline, before the second PIPAC procedure (approximately 6 weeks after randomization), and at interval cytoreductive surgery (approximately 9 to 12 weeks after randomization)
Quality of life	Quality of life assessed using EORTC questionnaires during protocol follow-up.	During follow-up, assessed every 3 months for 2 years after completion of treatment Quality of life is included as a protocol-defined follow-up assessment and is also listed among the correlative studies.

Collaborators and Investigators

• Sponsor: Moscow Regional Oncological Dispensary
• Investigators: Principal Investigator: Alexey S. Dzasokhov, MD, PhD, Moscow Regional Oncological Dispensary; Study Chair: Sergei O. Gunyakov, Moscow Regional Oncological Dispensary

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2025
• Primary Completion (Estimated): October 2, 2026
• Study Completion (Estimated): April 2, 2030

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Peritoneal carcinomatosis; Intraperitoneal chemotherapy; First-line treatment; PIPAC; Pressurized intraperitoneal aerosol chemotherapy; Advanced epithelial ovarian cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Abdominal Neoplasms; Peritoneal Neoplasms
• Other Study ID Numbers: PIPAC-NOVA.0221042025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No