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

NCT04811703 | Recruiting Phase 1 DMC

• 2 other identifiers: 69HCL20_09202024-515996-37-00
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Metastatic Ovarian Carcinoma; Peritoneal Carcinomatosis; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Stage III Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Metastatic Malignant Neoplasm in the Peritoneum

Keywords

Dose escalation; Phase I study; Intravenous Chemotherapy; Intraperitoneal chemotherapy; PIPAC; RP2D; cytoreductive surgery; Ovarian epithelial cancer; peritoneal cancer; doxorubicin; cisplatin; CA-125 antigen; pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities

  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 Outcomes (8)

• Rate of complete surgical resection

  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

  After completing chemotherapy treatment, at 4 to 5 weeks after the third cycle of post PIPAC (each cycle is 28 days)

• Peritoneal cancer index (PCI) evolution

  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

  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.

• Change in CA-125 concentration

  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)

Study Arms (1)

Combined PIPAC / IV chemotherapy treatment

EXPERIMENTAL

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

Interventions

Combined PIPAC / IV chemotherapy treatment DRUG

Addition of cisplatin-doxorubicin (with or without sodium thiosulfate according to the cisplatin dose level) PIPAC sessions to carboplatin-paclitaxel systemic Chemotherapy

Combined PIPAC / IV chemotherapy treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Inability to comply with study follow-up for geographical, social, or psychological reasons, as judged by the investigator.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (6)

Hôpital Claude Huriez - Chirurgie générale et digestive

Lille, France

RECRUITING

Hôpital Claude Huriez - Oncologie médicale

Lille, France

RECRUITING

Hôpital de la Croix-Rousse

Lyon, France

RECRUITING

Hôpital Lyon Sud - Chirurgie Digestive et Oncologique

Pierre-Bénite, 69495, France

RECRUITING

Hôpital Lyon Sud - Chirurgie Gynécologique et oncologique-obstétrique

Pierre-Bénite, France

RECRUITING

Hôpital Lyon Sud - Oncologie Médicale

Pierre-Bénite, France

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Peritoneal Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Fallopian Tube Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Justine ARQUILLIERE, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Justine ARQUILLIERE, MD

CONTACT

04 78 86 23 71; justine.arquilliere@chu-lyon.fr

Naoual BAKRIN, MD

CONTACT

04 78 86 23 71; naoual.bakrin@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 23, 2021
• Study Start: July 30, 2021
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

FR (6)