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

NCT ID: NCT04811703

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-30
• Study Completion Date: 2027-01-31

Brief 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).

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).

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combined PIPAC / IV chemotherapy treatment

Patients will undergo 3 cycles of combined chemotherapy, consisting of PIPAC (cisplatin-doxorubicin, escalating doses) and systemic chemotherapy (paclitaxel-carboplatine, standard doses). First patient will be treated at the lowest dose: doxorubicin 2.1 mg/m² and cisplatin 10.5 mg/m². Subsequent patients will be treated at the dose recommended by the CRM algorithm in the absence of dose-limiting toxicity. A total of 11 dose levels with a factor between 1 and 3 are considered. The maximum dose considered will be doxorubicin, 6.3 mg/m² and cisplatin, 31.5 mg/m². The doses of intravenous chemotherapy will be defined in a standard way, according to the habits of the investigating clinicians and in accordance with the doses received previously. Each cycle will last 28 days and will begin at day 1 with PIPAC procedure and will be completed at day 8 with systemic chemotherapy. Combined chemotherapy will be repeated every 4 weeks for up to 3 cycles in the absence of unacceptable toxicity.

Group Type: EXPERIMENTAL

Combined PIPAC / IV chemotherapy treatment

Intervention Type: DRUG

Addition of cisplatin-doxorubicin PIPAC sessions to carboplatin-paclitaxel systemic Chemotherapy

Interventions

Combined PIPAC / IV chemotherapy treatment

Addition of cisplatin-doxorubicin PIPAC sessions to carboplatin-paclitaxel systemic Chemotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years and ≤ 75 years
• ECOG PS 0-2 ;
• Epithelial stage IIb to IVa carcinoma of the ovary, fallopian tubes, or peritoneum proven histologically, stage III or IV of the FIGO classification and with history of insufficient tumor response/ after three cycles of previous neoadjuvant systemic carboplatin-paclitaxel chemotherapy as judged by the investigators after discussion and validation in Multidisciplinary Team ;
• Adequate hematologic function
• Absolute Neutrophil Count > 1500 / mm3 (or 1.5 10 9/L)
• Hemoglobin ≥ 9.0 g/dL,
• platelets > 100 G/L,
• Adequate hepatic and renal function:
• Serum creatinine ≤1.5 times upper normal values or glomerular filtration rate ≥ 60 mL/min/1.73 m2 estimated by the CKD-EPI equation
• Total bilirubin ≤1.5 times the upper normal limit,
• ASAT / ALAT ≤1.5 times the upper normal limit (≤5 times upper normal limits for patients with liver metastases);
• Absence of unstable pathologies : myocardial infarction within 6 months prior to the start of the study, congestive heart failure, unstable angina, active cardiomyopathy, unstable rhythm disorder, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer, or any pathology that could be aggravated by treatment or limit compliance (investigator's judgment)
• Patient information given and Written informed consent obtained prior to the initiation of any specific study procedure
• Affiliated to a social insurance regime or similar

Exclusion Criteria

• Extra-peritoneal metastases (position or number which make the disease unresectable)
• Signs of intestinal obstruction or lesions with risk of intestinal perforation, or signs of inflammatory disease of the digestive tract
• Contraindication to systemic chemotherapy CARBOPLATIN-PACLITAXEL :known allergy to paclitaxel
• Contraindication to the PIPAC procedure:
• Known allergy to cisplatin or other platinum-containing compounds
• Known allergy to doxorubicin or other anthracyclines or anthracenediones;
• Heart failure with myocardial insufficiency
• Uncontrolled coronary insufficiency;
• Pregnancy or breastfeeding
• Persons deprived of liberty or under guardianship ;
• Major patient protected by the Law;
• Persons participating in other research with an exclusion period still in progress at the time of inclusion or research that may interfere with the results of the present study (investigator's judgment) ;
• Impossibility to submit to the medical follow-up of the trial for geographical, social or psychic reasons (investigator's judgement)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Justine ARQUILLIERE, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Hôpital Claude Huriez - Chirurgie générale et digestive

Lille, , France

Site Status: RECRUITING

Hôpital Claude Huriez - Oncologie médicale

Lille, , France

Site Status: RECRUITING

Hôpital de la Croix-Rousse

Lyon, , France

Site Status: RECRUITING

Hôpital Lyon Sud - Chirurgie Digestive et Oncologique

Pierre-Bénite, , France

Site Status: RECRUITING

Hôpital Lyon Sud - Chirurgie Gynécologique et oncologique-obstétrique

Pierre-Bénite, , France

Site Status: RECRUITING

Hôpital Lyon Sud - Oncologie Médicale

Pierre-Bénite, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Justine ARQUILLIERE, MD

Role: CONTACT

justine.arquilliere@chu-lyon.fr

04 78 86 23 71 ext. +33

Naoual BAKRIN, MD

Role: CONTACT

naoual.bakrin@chu-lyon.fr

04 78 86 23 71 ext. +33

Facility Contacts

Clarisse EVENO, MD

Role: primary

Clarisse.EVENO@CHRU-LILLE.FR

Anne PLOQUIN, MD

Role: primary

anne.ploquin@CHRU-LILLE.FR

Sophie DUPLOMB, MD

Role: primary

sophie.duplomb@chu-lyon.fr

04 26 73 26 12 ext. +33

Naoual BAKRIN, MD

Role: primary

naoual.bakrin@chu-lyon.fr

04 78 86 23 71

Naoual BAKRIN, MD

Role: primary

naoual.bakrin@chu-lyon.fr

Naoual BAKRIN, MD

Role: primary

naoual.bakrin@chu-lyon.fr

Other Identifiers

69HCL20_0920

Identifier Type: -

Identifier Source: org_study_id