Peritoneal Metastases from Colorectal Cancer
Conditions
Keywords
Surgical oncology, Peritoneal metastasis, Pressurized IntraPeritoneal Aerosol Chemotherapy, Systemic chemotherapy
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
Interventions
DRUGStandard 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.
PROCEDUREPIPAC
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.
Sponsors
Institut Cancerologie de l'Ouest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) between the two groups | From 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
| Measure | Time frame | Description |
|---|---|---|
| EORTC QLQ-C30 questionnaire | At 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 questionnaire | At 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 |
| Overall survival (OS) between the two groups | From randomisation to 18 months after last patient randomisation | Overall survival (OS) defined as the time between randomisation and death from any cause |
| Obstruction-free survival (OFS) between the two groups | From 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 response | At 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. |
| Peritoneal progression free survival (PPFS) between the two groups | From 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. |
Countries
France
Contacts
Primary ContactFrédéric DUMONT, MD
Backup ContactEmilie DEBEAUPUIS
Outcome results
None listed