Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Associated With Systemic Chemotherapy in Women With Advanced Ovarian Cancer (PIPACOVA)

May 18, 2026 updated by: Hospices Civils de Lyon

Phase I Dose Escalation Study Evaluating the Safety of Adding Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) With Cisplatin-doxorubicin to the Systemic Chemotherapy, and the Recommended Phase II Dose, in Women With Insufficient Response to Carboplatin-paclitaxel for Advanced Epithelial Cancer of the Ovary, Fallopian Tubes or Peritoneum

Women with a history of tumor response insufficient to allow complete cytoreductive surgery after three cycles of prior neoadjuvant systemic carboplatin-paclitaxel chemotherapy will be prospectively enrolled in this phase I study. After providing written informed consent and confirmation of unresectable disease by multidisciplinary assessment, patients will undergo three cycles of combined chemotherapy consisting of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with doxorubicin and cisplatin at escalating dose levels, combined with systemic intravenous chemotherapy using carboplatin and paclitaxel at standard doses. Treatment cycles will last 28 days, with PIPAC administered on Day 1 and systemic chemotherapy on Day 8, for a maximum of three cycles in the absence of unacceptable toxicity.

Dose escalation of PIPAC chemotherapy will follow a Continual Reassessment Method (CRM) algorithm. The first patient will be treated at the lowest dose level, and subsequent patients will receive the recommended dose according to the CRM, conditional on the occurrence of dose-limiting toxicity (DLT) observed during Cycle 1. From dose level 7 onward, corresponding to cisplatin and doxorubicin doses associated with an increased risk of renal toxicity, sodium thiosulfate will be systematically administered prior to each PIPAC procedure for its nephroprotective effect, in accordance with the cisplatin dose level and current clinical practice.

The primary objective of the study is to determine the maximum tolerated dose (MTD) of doxorubicin-cisplatin administered by PIPAC and to define the recommended dose for a subsequent phase II trial. DLTs will be actively collected and reviewed as soon as they are identified during the first treatment cycle.

Secondary objectives include evaluation of pathological response, radiological tumor response, and changes in the extent of peritoneal disease following combined chemotherapy, as well as characterization of the pharmacokinetics of PIPAC-administered drugs. Additional exploratory objectives include assessment of the KELIM parameter as a predictive marker of sensitivity to combined chemotherapy and evaluation of the overall safety profile of the treatment strategy.

On Day 1 of the first treatment cycle, blood samples will be collected for pharmacokinetic analysis of doxorubicin and cisplatin. Serum CA-125 levels will be measured before each intraperitoneal or intravenous chemotherapy administration throughout the study. At the end of combined chemotherapy, radiological tumor assessment by CT scan or MRI and a final CA-125 measurement will be performed. Patients achieving complete response, partial response, or stable disease according to RECIST v1.1 criteria will undergo re-evaluation for surgical resectability. If complete cytoreductive surgery is deemed feasible, surgery will be scheduled with a post-operative follow-up visit planned one month later. Patients with progressive or persistently unresectable disease will discontinue study participation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Lille, France
        • Recruiting
        • Hôpital Claude Huriez - Chirurgie générale et digestive
        • Principal Investigator:
          • Clarisse EVENO, MD
        • Contact:
      • Lille, France
        • Recruiting
        • Hôpital Claude Huriez - Oncologie médicale
        • Contact:
        • Principal Investigator:
          • Anne PLOQUIN, MD
      • Lyon, France
        • Recruiting
        • Hopital de la Croix-Rousse
        • Contact:
        • Principal Investigator:
          • Sophie DUPLOMB, MD
      • Pierre-Bénite, France, 69495
        • Recruiting
        • Hôpital Lyon Sud - Chirurgie Digestive et Oncologique
        • Contact:
        • Principal Investigator:
          • Justine ARQUILLIERE, MD
      • Pierre-Bénite, France
        • Recruiting
        • Hôpital Lyon Sud - Chirurgie Gynécologique et oncologique-obstétrique
        • Contact:
        • Principal Investigator:
          • Witold GERTYCH, MD
      • Pierre-Bénite, France
        • Recruiting
        • Hôpital Lyon Sud - Oncologie Médicale
        • Contact:
        • Principal Investigator:
          • Benoit YOU, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years and ≤ 75 years;
  • ECOG Performance Status 0-2;
  • Histologically confirmed epithelial carcinoma of the ovary, fallopian tubes, or peritoneum, FIGO stage IIb to IVa, with a tumor response after three cycles of carboplatin-paclitaxel that does not correspond to disease progression but is insufficient to allow complete cytoreductive surgery, as assessed by the investigators after multidisciplinary tumor board discussion and validation;

  • Adequate hematological function:

    • Absolute neutrophil count > 1,500/mm³ (or 1.5 × 10⁹/L);
    • Hemoglobin ≥ 9.0 g/dL;
    • Platelet count > 100 × 10⁹/L;

  • Adequate renal and hepatic function:

    • Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or estimated glomerular filtration rate ≥ 60 mL/min/1.73 m² (CKD-EPI equation);
    • Total bilirubin ≤ 1.5 × ULN;
    • AST and ALT ≤ 1.5 × ULN (≤ 5 × ULN in patients with liver metastases);
  • No unstable medical conditions, including myocardial infarction within 6 months prior to study entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer disease, or any condition that could be worsened by the study treatment or impair compliance, as judged by the investigator;
  • Written informed consent obtained prior to any study-specific procedures;
  • Patient affiliated with a national health insurance system.

Exclusion Criteria:

  • Extra-peritoneal metastases whose location or extent precludes a potentially curative surgical procedure;
  • Signs of bowel obstruction, bowel lesions with a high risk of intestinal perforation based on their location, or evidence of inflammatory bowel disease;
  • Contraindication to intravenous carboplatin-paclitaxel chemotherapy, including known severe hypersensitivity to paclitaxel;

  • Contraindication to PIPAC procedures, including:

    • Known hypersensitivity to cisplatin or other platinum compounds;
    • Known hypersensitivity to doxorubicin or other anthracyclines or anthracenediones;
    • Cardiac disease with myocardial insufficiency;
    • Uncontrolled coronary artery disease;
  • Known hypersensitivity to sodium thiosulfate, sulfites, or any of its excipients;
  • Administration of a live attenuated vaccine within 3 months prior to study treatment initiation or planned during the study;
  • Pregnant or breastfeeding women;
  • Individuals deprived of liberty, under guardianship, or subject to legal protection measures;
  • Participation in another interventional research study with an ongoing exclusion period at inclusion, or in a study that could interfere with the results of the present study, as judged by the investigator;
  • Inability to comply with study follow-up for geographical, social, or psychological reasons, as judged by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined PIPAC / IV chemotherapy treatment
Participants will receive up to three cycles of combined chemotherapy within a single treatment arm. Each 28-day cycle consists of PIPAC with escalating doses of cisplatin and doxorubicin (Day 1) combined with systemic chemotherapy using paclitaxel and carboplatin at standard doses (Day 8). The first patient will receive doxorubicin 2.1 mg/m² and cisplatin 10.5 mg/m²; dose escalation will follow a CRM algorithm in the absence of dose-limiting toxicity. Eleven dose levels are planned, up to a maximum of doxorubicin 6.3 mg/m² and cisplatin 31.5 mg/m². From dose level 7 onward, and for patients enrolled after approval of Amendment No. 7, sodium thiosulfate 25% will be administered prior to each PIPAC procedure (9 g/m² over 20 min with cisplatin, then 12 g/m² over 6 h). Treatment will be repeated every 4 weeks for up to three cycles unless unacceptable toxicity occurs.
Drug: Combined PIPAC / IV chemotherapy treatment
Addition of cisplatin-doxorubicin (with or without sodium thiosulfate according to the cisplatin dose level) PIPAC sessions to carboplatin-paclitaxel systemic Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicities
Time Frame: First cycle of combined chemotherapy = day 1 up to day 28 of the first cycle

Dose-limiting toxicities will be defined as any of the following events observed during the first cycle of treatment and judged by the investigator to be possibly related to the treatment, based on the classification of the National Cancer Institute Common Criteria for Adverse Events Terminology (NCI CTCAE) Version 5.0 :

  • Grade 4 Neutropenia (absolute neutrophil count <500 /mm3 (or 0.5 109/L)) ≥7 consecutive days;
  • Neutropenia of grade ≥ 3 (absolute neutrophil count <1000 /mm3 (or 1 109/L)) and temperature ≥ 38.5°C ;
  • Thrombocytopenia grade 4 (<25,000/mm3 platelets (or 25 109/L)) or grade 3 (< 50,000/mm3 (or 50 109/L)) associated with bleeding ;
  • Non-hematological toxicity of grade ≥3 (excluding non-life-threatening toxicities such as alopecia, asymptomatic hypophosphatemia, etc.) despite adequate medical intervention judged by the investigator
First cycle of combined chemotherapy = day 1 up to day 28 of the first cycle

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of complete surgical resection
Time Frame: During cytoreductive surgery performed at the end of cycle 3 of combined chemotherapy (each cycle is 28 days), and at a maximum of 12 weeks after the third cycle of PIPAC

Assessed during cytoreductive surgery by the Completeness Cytoreduction (CC) score after the 3 cycles of combined chemotherapy.

Complete cytoreduction refers to a CC-0 or CC-1 score whereas a CC-2 or 3 score is classified as incomplete ; CC-0 score indicates no evidence of macroscopic disease after cytoreduction, a CC-1 score indicates persisting microscopic disease (tumour nodules are < 2.5 mm), a CC-2 score indicates persisting macroscopic disease (residual tumour nodules between 2.5 mm and 2.5 cm) and finally a CC-3 score indicates tumour nodules > 2.5 cm or a confluence of unresected tumour.
During cytoreductive surgery performed at the end of cycle 3 of combined chemotherapy (each cycle is 28 days), and at a maximum of 12 weeks after the third cycle of PIPAC
Proportion of complete, partial or stabilized tumor response
Time Frame: After completing chemotherapy treatment, at 4 to 5 weeks after the third cycle of post PIPAC (each cycle is 28 days)
Assessed according to the Response Evaluation Criteria in Solid Tumor (RECIST) criteria version 1.1, on thoracic abdominal pelvic imaging (scanner or MRI in case of contraindication).
After completing chemotherapy treatment, at 4 to 5 weeks after the third cycle of post PIPAC (each cycle is 28 days)
Change in CA-125 concentration
Time Frame: Pharmacokinetic blood samples for each cycle, each cycle being 28 days (at day 1 for PIPAC chemotherapy; at day 8 for systemic chemotherapy) and before post-treatment laparoscopy at 4-5 weeks after the third PIPAC)
CA-125 evolution profile will be monitored during chemotherapy and before surgery of reevaluation at post-treatment visit. Then, mathematical modeling of CA-125 elimination rate KELIM will be calculated from individual CA-125 levels.
Pharmacokinetic blood samples for each cycle, each cycle being 28 days (at day 1 for PIPAC chemotherapy; at day 8 for systemic chemotherapy) and before post-treatment laparoscopy at 4-5 weeks after the third PIPAC)
Rates of adverse events and operative complications
Time Frame: Up to 8 months after inclusion
Adverse events according to the NCI CTCAE v5.0 classification (including toxicities) and per- and post-operative complications according to the Clavien-Dindo classification.
Up to 8 months after inclusion
Peritoneal cancer index (PCI) evolution
Time Frame: At day 1 of the beginning of each cycle during PIPAC procedure, at 4 to 5 weeks post PIPAC cycle 3 (each cycle is 28 days) and during post-treatment laparoscopy and/or during cytoreductive surgery (12 weeks max post PIPAC cycle 3)]
PCI index will be evaluated under videosurveillance during laparoscopy. PCI is determined according to Sugarbaker, based on lesion size and distribution. Using a pictorial of the abdomen, each location of a 13 point list receives a peritoneal cancer grade ranging from 0 to 3. The counts for all 13 locations are then summarized as PCI.
At day 1 of the beginning of each cycle during PIPAC procedure, at 4 to 5 weeks post PIPAC cycle 3 (each cycle is 28 days) and during post-treatment laparoscopy and/or during cytoreductive surgery (12 weeks max post PIPAC cycle 3)]
Area under the curve (AUC) for plasma concentration of DOXORUBICIN and CISPLATIN
Time Frame: During day 1 of the first cycle of PIPAC chemotherapy (at 0, 30 minute, 1 hour, 2 hours, 4 hours, 6 hours, 7/8 hours and 24 hours post PIPAC for the both chemotherapeutic compound and 48 hours only for DOXORUBICIN), each cycle being 28 days.
The plasma biodisponibility of the PIPAC doxorubicin and CISPLATIN (total and ultrafilterable platinum) chemotherapeutic compound will be assessed by reporting the Area under the plasma concentration- time curve.
During day 1 of the first cycle of PIPAC chemotherapy (at 0, 30 minute, 1 hour, 2 hours, 4 hours, 6 hours, 7/8 hours and 24 hours post PIPAC for the both chemotherapeutic compound and 48 hours only for DOXORUBICIN), each cycle being 28 days.
Evaluation of sodium thiosulfate-associated nephroprotection during PIPAC procedures : Change in serum creatinine levels
Time Frame: From baseline to after each PIPAC procedure, assessed at the end of each treatment cycle (each cycle defined as 28 days), for up to 3 cycles
Serum creatinine levels will be measured before each treatment (PIPAC or intravenous chemotherapy) and after each PIPAC procedure.
From baseline to after each PIPAC procedure, assessed at the end of each treatment cycle (each cycle defined as 28 days), for up to 3 cycles
Evaluation of sodium thiosulfate-associated nephroprotection during PIPAC procedures : Change in estimated glomerular filtration rate (eGFR)
Time Frame: From baseline to after each PIPAC procedure, assessed at the end of each treatment cycle (each cycle defined as 28 days), for up to 3 cycles
Estimated glomerular filtration rate (eGFR) will be measured before each treatment (PIPAC or intravenous chemotherapy) and after each PIPAC procedure.
From baseline to after each PIPAC procedure, assessed at the end of each treatment cycle (each cycle defined as 28 days), for up to 3 cycles

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Justine ARQUILLIERE, MD, Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2021

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

March 8, 2021

First Submitted That Met QC Criteria

March 19, 2021

First Posted (Actual)

March 23, 2021

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL20_0920
  • 2024-515996-37-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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