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

Phase 2
Not yet recruiting
Conditions
Peritoneal Metastases from Colorectal Cancer
Interventions
Drug: Standard Medical Therapy
Procedure: PIPAC
Registration Number
NCT06681038
Lead Sponsor
Institut Cancerologie de l'Ouest
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
114
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control ARMStandard Medical TherapySystemic treatments
Experimental ARMStandard Medical TherapyPIPAC procedure with pressurized aerosol containing oxaliplatin.
Experimental ARMPIPACPIPAC procedure with pressurized aerosol containing oxaliplatin.
Primary Outcome Measures
NameTimeMethod
Progression free survival (PFS) between the two groupsFrom randomisation to 18 months after last patient randomisation

Progression free survival (PFS) is defined as the time (in months) from randomisation until the date of progression or death from any cause.

Secondary Outcome Measures
NameTimeMethod
Overall survival (OS) between the two groupsFrom randomisation to 18 months after last patient randomisation

Overall survival (OS) defined as the time between randomisation and death from any cause

EORTC QLQ-C30 questionnaireAt enrollment, week 16 and week 32 after the start of treatment

Quality of life between the two groups evaluated by the score of EORTC QLQ-C30 questionnaire

EORTC QLQ-CR29 questionnaireAt enrollment, week 16 and week 32 after the start of treatment

Quality of life between the two groups evaluated by the scores of EORTC QLQ-CR29 questionnaire

Peritoneal progression free survival (PPFS) between the two groupsFrom randomisation to 18 months after last patient randomisation

Peritoneal progression free survival defined as the time between the date of randomisation and the date of peritoneal progression or death from any cause.

Obstruction-free survival (OFS) between the two groupsFrom randomisation to 18 months after last patient randomisation

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.

Histological tumor responseAt the end of the 12th course of treatment (week 24)

Peritoneal regression grading score (PRGS) on biopsies performed at surgical exploration in both groups, and systematically during 1st and 2nd PIPAC procedure.

Trial Locations

Locations (15)

Centre François Baclesse

🇫🇷

Caen, France

Centre Georges François Leclerc

🇫🇷

Dijon, France

CHU

🇫🇷

Lille, France

CHU Dupuytren

🇫🇷

Limoges, France

APHM La Timone

🇫🇷

Marseille, France

Institut de Cancérologie de Montpellier (ICM)

🇫🇷

Montpellier, France

APHP Saint Louis

🇫🇷

Paris, France

APHP Hôpital Européen Georges Pompidou

🇫🇷

Paris, France

Hospices Civils de Lyon - Hôpital Lyon Sud

🇫🇷

Pierre-Bénite, France

Institut de Cancérologie de l'Ouest - Saint Herblain

🇫🇷

Saint HERBLAIN, France

Hôpital d'Instruction des Armées Bégin

🇫🇷

Saint Mande, France

CHRU

🇫🇷

Strasbourg, France

Centre Hospitalier TARBES

🇫🇷

Tarbes, France

Institut de Cancérologie de Lorraine (ICL)

🇫🇷

Vandoeuvre Les Nancy, France

Gustave Roussy

🇫🇷

Villejuif, France

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