Systemic Antitumor Treatment with or Without Pressurized Intraperitoneal Aerosol Chemotherapy for Colon Peritoneal Metastases (PIPOX02) (PIPOX02)

Systemic Antitumor Treatment with or Without Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Colon Peritoneal Metastases - a Multicentre Phase II Randomized Trial (PIPOX02)

The goal of this clinical trial is to learn if Pressurized intraperitoneal aerosol chemotherapy (PIPAC) significantly improve the progression-free survival (PFS) in patients with advanced peritoneal metastasis from colorectal cancer.

Researchers will compare 2 strategies, systemic treatments (chemotherapy + targeted therapy) corresponding to standard treatment with or without intraperitoneal oxaliplatin (PIPAC) to see if PIPAC improve the progression-free survival.

Participants will:

• receive a standard treatment every 2 weeks for 12 cycles of intravenous FOLFIRI or FOLFIRINOX + targeted systemic therapy (anti-EGFR or anti-VEGF) in the both arms.
• receive up to a maximum of 4 PIPAC every 6 weeks with pressurized aerosol containing oxaliplatin in experimental arm.
• receive a maintenance treatment until progression or until the onset of severe toxicity after 12 cycles.
• be asked to perform a CT scan and carcinoembryonic antigen (CEA) assay every 8 weeks until progression

Study Overview

• Status: Not yet recruiting
• Conditions: Peritoneal Metastases from Colorectal Cancer
• Intervention / Treatment: Drug: Standard Medical Therapy; Procedure: PIPAC

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Frédéric DUMONT, MD; Phone Number: +33240679900; Email: frédéric.dumont@ico.unicancer.fr
• Study Contact Backup: Name: Emilie DEBEAUPUIS; Phone Number: +33240679844; Email: emilie.debeaupuis@ico.unicancer.fr

Study Locations

• France
  • Caen, France, 14076
    • Centre Francois Baclesse
    • Contact: Sharmini VARATHARAJAH, MD
    • Contact: Sharmini VARATHARAJAH, MD; Phone Number: +33231455002; Email: s.varatharajah@baclesse.unicancer.fr
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
    • Contact: David ORRY, MD; Phone Number: +33380737508; Email: dorry@cgfl.fr
    • Contact: David ORRY, MD
  • Lille, France, 59045
    • CHU
    • Contact: Clarisse EVENO, MD; Phone Number: +33320445506; Email: clarisse.eveno@chu-lille.fr
    • Contact: Clarisse EVENO, MD
  • Limoges, France, 87042
    • CHU Dupuytren
    • Contact: Sylvaine DURAND, MD; Phone Number: +33699022340; Email: sylvaine.durand-fontanier@chu-limoges.fr
    • Contact: Sylvaine DURAND, MD
  • Marseille, France, 13385
    • APHM La Timone
    • Contact: Nicolas PIRRO, MD; Phone Number: +33491388487; Email: nicolas.pirro@ap-hm.fr
    • Contact: Nicolas PIRRO, MD
  • Montpellier, France, 34298
    • Institut de Cancérologie de Montpellier (ICM)
    • Contact: Olivia SGABURA, MD; Phone Number: +33467613103; Email: olivia.sgarbura@icm.unicancer.fr
    • Contact: Olivia SGABURA, MD
  • Paris, France, 75010
    • APHP Saint Louis
    • Contact: Diane GOERE, MD; Phone Number: +33142499718; Email: diane.goere@aphp.fr
    • Contact: Diane GOERE, MD
  • Paris, France, 75015
    • APHP Hopital Européen Georges Pompidou
    • Contact: Antoine MARIANI, MD; Phone Number: +33156093562; Email: antoine.mariani@aphp.fr
    • Contact: Antoine MARIANI, MD
  • Pierre-Bénite, France, 69495
    • Hospices Civils de Lyon - Hôpital Lyon Sud
    • Contact: Vahan KEPENEKIAN, MD; Phone Number: +33478862371; Email: vahan.kepenekian@chu-lyon.fr
    • Contact: Vahan KEPENEKIAN, MD
  • Saint HERBLAIN, France, 44805
    • Institut de Cancérologie de l'Ouest - Saint Herblain
    • Contact: Frédéric DUMONT, MD; Phone Number: +33240679900; Email: frédéric.dumont@ico.unicancer.fr
    • Contact: Frédéric DUMONT, MD
  • Saint Mande, France, 94160
    • Hopital d'Instruction des Armees BEGIN
    • Contact: Anne-Cécile EZANNO, MD; Phone Number: +33143985250; Email: ezanno.annececile@gmail.com
    • Contact: Anne-Cécile EZANNO, MD
  • Strasbourg, France, 67098
    • CHRU
    • Contact: Cécile BRIGAND, MD; Phone Number: +33388126085; Email: cecile.brigand@chru-strasbourg.fr
    • Contact: Cécile BRIGAND, MD
  • Tarbes, France, 65013
    • Centre Hospitalier TARBES
    • Contact: Amandine PINTO, Doctor; Email: apinto@ch-tarbes-vic.fr
    • Contact: Phone Number: +33562546231
    • Contact: Amandine PINTO, MD
  • Vandoeuvre Les Nancy, France, 54500
    • Institut de Cancérologie de Lorraine (ICL)
    • Contact: Cécilia CERIBELLI, MD
    • Contact: Cécilia CERIBELLI, MD; Phone Number: +33383598451; Email: c.cerribelli@nancy.unicancer.fr
  • Villejuif, France, 94805
    • Gustave Roussy
    • Contact: Isabelle SOURROUILLE, MD; Phone Number: +33142114350; Email: isabelle.sourrouille@gustaveroussy.fr
    • Contact: Isabelle SOURROUILLE, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ECOG performance status of 0 to 2;
• Histopathologically confirmed colonic adenocarcinoma with synchronous or metachronous peritoneal metastasis (PM);

• Unresectable PM defined as any of the following:

  • PCI >15
  • Extended small bowell involvement
  • Poor general condition contra-indication to a major abdominal surgery (eg: a complete cytoreductive surgery), as decided by the medico-surgical team of the investigator's site specialised in peritoneal carcinomatosis in charge of the patient.
• A surgical exploration performed less than 4 weeks before inclusion (if not, a laparoscopic exploration must be performed);
• First line systemic chemotherapy for advanced / metastatic colonic adenocarcinoma. Systemic chemotherapy in an adjuvant setting is allowed if completed more than 6 months before recurrence and without persistent oxaliplatin-induced neuropathy;
• No extended intraperitoneal adherences defined by at least 9 out of 13 abdominal regions correctly explored during surgical exploration (laparoscopy or laparotomy;

Exclusion Criteria:

• Other cancer treated within the last 3 years, with the exception of in situ cervical carcinoma or basocellular carcinoma;
• Rectal cancer primary (tumor <15 cm from the anal verge);
• Mutational status corresponding to microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR);
• Complete or partial bowel obstruction unresponsive to medical treatment;
• Extraperitoneal polymetastatic diseases. (Only oligometastatic1 diseases are allowed for inclusion);
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months prior to enrolment;
• Active gastrointestinal bleeding;
• Inflammatory bowel disease;
• Peripheral neuropathy according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0, grade ≥2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control ARM; Systemic treatments	Drug: Standard Medical Therapy; Intravenous doublet chemotherapy FOLFIRI or FOLFIRINOX + targeted systemic therapy (anti-EGFR or anti-VEGF). Administered every 2 weeks for 12 cycles. Dosage and administration at recommended doses.
Experimental: Experimental ARM; PIPAC procedure with pressurized aerosol containing oxaliplatin.	Drug: Standard Medical Therapy; Intravenous doublet chemotherapy FOLFIRI or FOLFIRINOX + targeted systemic therapy (anti-EGFR or anti-VEGF). Administered every 2 weeks for 12 cycles. Dosage and administration at recommended doses.; Procedure: PIPAC; In addition to standard systemic treatment, patients receive also four PIPAC procedures with pressurized aerosol containing oxaliplatin. The PIPAC procedure is repeated up to a maximum of 4 times every 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) between the two groups	Progression free survival (PFS) is defined as the time (in months) from randomisation until the date of progression or death from any cause.	From randomisation to 18 months after last patient randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS) between the two groups	Overall survival (OS) defined as the time between randomisation and death from any cause	From randomisation to 18 months after last patient randomisation
EORTC QLQ-C30 questionnaire	Quality of life between the two groups evaluated by the score of EORTC QLQ-C30 questionnaire	At enrollment, week 16 and week 32 after the start of treatment
EORTC QLQ-CR29 questionnaire	Quality of life between the two groups evaluated by the scores of EORTC QLQ-CR29 questionnaire	At enrollment, week 16 and week 32 after the start of treatment
Peritoneal progression free survival (PPFS) between the two groups	Peritoneal progression free survival defined as the time between the date of randomisation and the date of peritoneal progression or death from any cause.	From randomisation to 18 months after last patient randomisation
Obstruction-free survival (OFS) between the two groups	Obstruction-free survival is defined as the time between the date of randomisation and the appearance of gastrointestinal obstruction requiring medication with high dose of corticosteroïd (> 1mg/kg) or intervention as nasogastric decompression, intraluminal stenting, surgical bypass, or decompression stomy (gastrostomy or ileo/colostomy) or death.	From randomisation to 18 months after last patient randomisation
Histological tumor response	Peritoneal regression grading score (PRGS) on biopsies performed at surgical exploration in both groups, and systematically during 1st and 2nd PIPAC procedure.	At the end of the 12th course of treatment (week 24)

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Investigators: Principal Investigator: Frédéric DUMONT, MD, Institut de Cancérologie de l'Ouest

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Estimated): November 8, 2024

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 7, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Peritoneal metastasis; Systemic chemotherapy; Pressurized IntraPeritoneal Aerosol Chemotherapy; Surgical oncology
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: ICO-2023-14

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