The aim of this study is to assess whether there are differences in PERITONEAL RECURRENCE in patients with Colon Cancer Peritoneal Metastases treated with complete surgical resection and systemic chemotherapy, with (Group 1) or without (Group 2) HIPEC with Mitomycin-C.
CytoReductive Surgery (CRS) + Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), especially from the year 2000 onwards, has obtained unprecedented results in patients with low to moderate volume peritoneal metastases (PM) of colorectal cancer (CRC), so that it has gradually been accepted, even being considered the best treatment for these patients. However, the actual role of HIPEC as a necessary component of treatment is unknown, despite its proven experimental basis. The French PRODIGE 7 study, presented at ASCO in 2018 and published on January 2021, has raised doubts about the survival benefit of HIPEC. In this study, there was no difference in overall survival (OS) with or without HIPEC (with Oxaliplatin 30 minutes) after resection of PM-CRC. However, since its presentation, several methodological flaws have been identified: a short exposure time to Oxaliplatin, an overestimation of the effect of HIPEC on OS (18 months) considered for the sample calculation, or the choice of OS as the main endpoint (since HIPEC can reduce peritoneal relapses, while OS is also influenced by the systemic treatment received by all patients). Due to these shortcomings and some others, the results have not been assumed to be definitive. Therefore, the majority of units specialized in peritoneal surface malignancy, continue to consider HIPEC in these patients as a recommended option, usually changing Oxaliplatin for Mitomycin-C (MMC). With these premises we propose this multicenter Clinical Trial, correcting the retrospective defects of PRODIGE 7. To do this, the cytostatic used in HIPEC will be changed (MMC instead of oxaliplatin), the infusion time will be increased (from 30 to 90 minutes), rectal cancers are ruled out (only colon cancers will be included), cases with high peritoneal extension (PCI\> 20) will be avoided, those cases in which a complete CRS (CCS 0) is not achieved will be excluded, and the main objective will be the Peritoneal Recurrence Free Survival (RFS) instead of the OS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
216
In the arm with HIPEC, this will be performed with Mytomicin C, at a dose of 35 mg/m2 in peritoneal dialysis solution (2 liter/m2) for 90 minutes, with dose fractionation: 50% min 0, 25% min 30, 25% min 60
in the arm without HIPEC, only complete cytoreductive surgery will be performed
Peritoneal Recurrence Free Survival
From the date of surgery to the date of peritoneal recurrence or death, or to the end of follow-up
Time frame: 3 years
Global recurrence at any location (Disease Free Survival)
From the date of surgery to the date of recurrence at any site or death
Time frame: 3 years
Locoregional and distant recurrence rate (isolated or coincident, with or without simultaneous peritoneal recurrence)
From the date of surgery to the date of locoregional and/or distant recurrence
Time frame: 3 years
Postoperative complications (rate and severity grade)
Using the CTCAE v5.0 adverse event classification system, including those related to HIPEC.
Time frame: days 1-90 after surgery
Peritoneal and global recurrence rate according to stratified PCI
Rate of peritoneal and global recurrence in 3 subgroups of PCI ((1-10, 11-15, 16-20)
Time frame: 3 years
Overall survival
Months from from the day of treatment initiation (either neoadjuvant SCT or upfront CRS) to the date of death or to the end of follow-up.
Time frame: 3 years
Quality of Life with EORTC validated questionnaire Core 30 (QLQ-C30)
The QLQ-CR29 is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30. In fact, their numbering is consecutive (the last item of QLQ-C30 is number 30, being the first item of QLQ-CR29 number 31). Both have function and symptom scales/single-items. All of the scales and single-item measures range in score from 0 to 100. A high score for the functional scale and functional single-items represents a high level of functioning, whereas a high score for the symptom scales and symptom single-items represents a high level of symptomatology or problems.
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Hospital General Universitario de Elche
Elche, Alicante, Spain
RECRUITINGHospital Universitario Torrecárdenas
Almería, Almería, Spain
RECRUITINGComplejo Hospitalario Universitario de Badajoz
Badajoz, Badajoz, Spain
RECRUITINGHospital Sant Joan Despi Moises Broggi
Sant Joan Despí, Barcelona, Spain
RECRUITINGHospital General Universitario de Castellón
Castellon, Castellón, Spain
RECRUITINGConsorcio Hospitalario Provincial de Castellón
Castellon, Castellón, Spain
RECRUITINGHospital General Universitario de Ciudad Real
Ciudad Real, Ciudad Real, Spain
RECRUITINGHospital Universitario Reina Sofía
Córdoba, Córdoba, Spain
RECRUITINGHospital Universitario Donostia
San Sebastián, Gipuzkoa, Spain
ACTIVE_NOT_RECRUITINGHospital Universitario de Gran Canaria Doctor Negrín
Las Palmas de Gran Canaria, Gran Canaria, Spain
RECRUITING...and 21 more locations
Time frame: pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months
Quality of Life with EORTC validated questionnaire Colorectal Cancer Module (QLQ-CR29).
The QLQ-CR29 is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30. In fact, their numbering is consecutive (the last item of QLQ-C30 is number 30, being the first item of QLQ-CR29 number 31). Both have function and symptom scales/single-items. All of the scales and single-item measures range in score from 0 to 100. A high score for the functional scale and functional single-items represents a high level of functioning, whereas a high score for the symptom scales and symptom single-items represents a high level of symptomatology or problems.
Time frame: pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months