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

Official title

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

Overview

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

Interventions

• 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.

Primary outcome measures

• Progression free survival (PFS) between the two groups [Time frame: From randomisation to 18 months after last patient randomisation]

Secondary outcome measures (6)

• Overall survival (OS) between the two groups [Time frame: From randomisation to 18 months after last patient randomisation]
• EORTC QLQ-C30 questionnaire [Time frame: At enrollment, week 16 and week 32 after the start of treatment]
• EORTC QLQ-CR29 questionnaire [Time frame: At enrollment, week 16 and week 32 after the start of treatment]
• Peritoneal progression free survival (PPFS) between the two groups [Time frame: From randomisation to 18 months after last patient randomisation]
• Obstruction-free survival (OFS) between the two groups [Time frame: From randomisation to 18 months after last patient randomisation]
• Histological tumor response [Time frame: At the end of the 12th course of treatment (week 24)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 15 centers

• Centre François Baclesse — Caen
• Centre Georges François Leclerc — Dijon
• CHU — Lille
• CHU Dupuytren — Limoges
• APHM La Timone — Marseille
• Institut de Cancérologie de Montpellier (ICM) — Montpellier
• APHP Saint Louis — Paris
• APHP Hôpital Européen Georges Pompidou — Paris
• … and 7 more centers

Identifiers

NCT: NCT06681038 · ICO-2023-14

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗