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

Condition(s) studied

Investigational drug(s) / intervention(s)

Combined PIPAC / IV chemotherapy treatment: Addition of cisplatin-doxorubicin PIPAC sessions to carboplatin-paclitaxel systemic Chemotherapy Auxiliary treatment : Since amendment n°7,, sodium thiosufate thiosulfate as nephrtoxicity prevention during each PIPAC sessions

Study summary

Women with history of tumor response insufficient to allow complete cytoreductive surgery after three cycles of previous neoadjuvant systemic carboplatin-paclitaxel chemotherapy will be prospectively recruited in this trial. After signed consent and if unresectability is confirmed, patients will undergo three cycles of doxorubicin-cisplatin PIPAC chemotherapy associated with systemic carboplatin-paclitaxel chemotherapy (alternating PIPAC and intravenous chemotherapy sessions over 3 cycles of 4 weeks).

Since the 7th amendment of the study, sodium thiosulfate as nephrtoxicity prevention has been administered concurrently with each PIPAC chemotherapy

The primary objective of the study is to determine the maximum tolerated dose (MDT).

During cycle 1, limiting dose toxicity must be collected as soon as it is known.

Each patients will be treated at the dose recommended by the CRM (Continual Reassessment Method ) algorithm conditional on dose-limiting toxicity during Cycle 1.

The dose escalation will be guided by CRM to determine the recommended dose of PIPAC chemotherapy for phase II trial.

Secondary objectives are :

* to evaluate the anatomopathological response, the radiologic tumoral response and the evolution of the peritoneal cancer extent, to the combined chemotherapy
* to describe the pharmacokinetic of the PIPAC chemotherapy
* to investigate the KELIM parameter as a predictive marker in the response sensitivity of the combined chemotherapy treatment
* and to evaluate the safety of the combined chemotherapy. During the first day of the first cycle, blood samples will be collected to measure doxorubicin and cisplatin (pharmacokinetic study). Along these 3 cycles, the dose of antigen CA-125 will be performed before each chemotherapies (intraperitoneal or intravenous).

Following the addition of sodium thiosulfate to the treatment regimen, an exploratory objective was added to assess its nephroprotective effects At the end of combined chemotherapy treatment, patients will undergo radiologic tumoral response by imaging assessment (scanner or MRI) and a last dosage of CA-125 will be realized..

In case of a complete / partial response / stabilization (RECIST criteria v.1.) on the imaging, re-evaluation for resectability will be done. If resectable disease, cytoreductive surgery will be programmed and a post-operative visit 1 month later will be realized. Otherwise for patients with progress disease or unresectable the participation in the study will be finished.

Eligibility

Primary outcome measure(s)

• Dose-limiting toxicities — First cycle of combined chemotherapy = day 1 up to day 28 of the first cycle
  Dose-limiting toxicities (DLTs) will be defined as any event occurring during the first treatment cycle and considered by the investigator as possibly related to treatment, according to NCI CTCAE v5.0. DLTs include: Grade 4 neutropenia (absolute neutrophil count \<500/mm³ \[0.5 × 10⁹/L\]) lasting ≥7 consecutive days; Grade ≥3 neutropenia (absolute neutrophil count \<1000/mm³ \[1 × 10⁹/L\]) associated with a temperature ≥38.5°C; Grade 4 thrombocytopenia (\<25,000/mm³ platelets \[25 × 10⁹/L\]) or Grade 3 thrombocytopenia (\<50,000/mm³ \[50 × 10⁹/L\]) associated with bleeding; Grade ≥3 non-hematological toxicity despite adequate medical intervention, excluding non-life-threatening toxicities such as alopecia or asymptomatic hypophosphatemia; and Grade ≥2 acute kidney injury according to the 2024 KDIGO classification, defined as at least a twofold increase in serum creatinine compared with baseline.

Trial sites (6)

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