Clinical Trial on HIPEC with Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)

Phase 4

Recruiting

• Conditions: Peritoneal Carcinomatosis; Colon Cancer
• Interventions: Drug: complete cytoreductive surgery plus HIPEC with Mytomicin C for 90 minutes; Procedure: complete cytoreductive surgery without HIPEC

• Registration Number: NCT05250648
• Lead Sponsor: Hospital Universitario de Fuenlabrada

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2022-01-23
• Study First Submitted QC: 2022-02-20
• Study First Posted: 2022-02-22
• Study Start: 2022-03-02
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-06
• Last Update Posted: 2024-10-09
• Primary Completion: 2029-10
• Study Completion: 2029-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 216

Inclusion Criteria

1. Histologically confirmed colon adenocarcinoma, except signet ring cell carcinomas (those with > 50% of the tumor composed of these cells, which comprise only 1% of all colon adenocarcinomas).
2. Absence of previously treated or current extraperitoneal metastases, including distant lymphadenopathy (retroperitoneal, mediastinal, etc), liver metastases, or lung metastases (ruled out by PET-scan in case of doubt).
3. Synchronous or metachronous peritoneal metastasis of mild to moderate volume, with a PCI ≤ 20 (Appendix 2) (intraoperative confirmation).
4. Macroscopically complete surgical cytoreduction CCS-0 (intraoperative confirmation).
5. Treatment with perioperative systemic chemotherapy (SCT), before and/or after surgical procedure.
6. Age> 18 years.
7. Acceptable anesthetic/surgical risk: ASA 1-3 (Appendix 3), ECOG 0-1 (Appendix 4). No severe alterations in hematological, renal, cardiac, pulmonary or hepatic function (operable patients).
8. Information to the patient and signing of a study-specific informed consent.

Exclusion Criteria

1. Peritoneal carcinomatosis of any other origin, particularly rectal cancer or appendicular adenocarcinoma, or signet ring cell colon cancer on histology.
2. No intraoperative confirmation of peritoneal disease (PCI 0). Likewise, cases of perianastomotic (local) or lymph node (locoregional) recurrences will be excluded.
3. High volume peritoneal disease with a PCI> 20 (intraoperative evaluation).
4. Concurrent or previously treated extraperitoneal disease.
5. Disease progression during preoperative chemotherapy, if received.
6. Patients previously treated with HIPEC.
7. History of other cancers (except cutaneous basal cell carcinoma or cervix carcinoma in situ) in the 5 years prior to entry into the study.
8. Patients included in another first-line clinical trial for the studied disease.
9. Pregnancy (or suspicion of it) or lactation period.
10. Emergency surgical intervention for obstruction or perforation of a primary tumour with synchronous PM (although rescue and secondary CRS + HIPEC after emergency surgery of the primary tumour are acceptable if inclusion criteria are fulfilled).
11. Persons deprived of liberty or under legal or administrative supervision.
12. Inability to understand the nature of the intervention, the risks, benefits, expected evolution and the need to undergo periodic medical examinations, either for geographical, social or psychological reasons.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
complete cytoreductive surgery plus HIPEC with Mytomicin C for 90 minutes	complete cytoreductive surgery plus HIPEC with Mytomicin C for 90 minutes	-
complete cytoreductive surgery without HIPEC	complete cytoreductive surgery without HIPEC	-

Primary Outcome Measures

Name	Time	Method
Peritoneal Recurrence Free Survival	3 years	From the date of surgery to the date of peritoneal recurrence or death, or to the end of follow-up

Secondary Outcome Measures

Name	Time	Method
Global recurrence at any location (Disease Free Survival)	3 years	From the date of surgery to the date of recurrence at any site or death
Locoregional and distant recurrence rate (isolated or coincident, with or without simultaneous peritoneal recurrence)	3 years	From the date of surgery to the date of locoregional and/or distant recurrence
Postoperative complications (rate and severity grade)	days 1-90 after surgery	Using the CTCAE v5.0 adverse event classification system, including those related to HIPEC.
Peritoneal and global recurrence rate according to stratified PCI	3 years	Rate of peritoneal and global recurrence in 3 subgroups of PCI ((1-10, 11-15, 16-20)
Overall survival	3 years	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.
Quality of Life with EORTC validated questionnaire Colorectal Cancer Module (QLQ-CR29).	pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months	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.
Quality of Life with EORTC validated questionnaire Core 30 (QLQ-C30)	pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months	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.

Trial Locations

Locations (31)

Hospital Regional Universitario de Málaga; 🇪🇸 Málaga, Spain

Hospital General Universitario de Elche; 🇪🇸 Elche, Alicante, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Sant Joan Despi Moises Broggi; 🇪🇸 Sant Joan Despí, Barcelona, Spain

Hospital General Universitario de Castellón; 🇪🇸 Castelló de la Plana, Castellón, Spain

Consorcio Hospitalario Provincial de Castellón; 🇪🇸 Castellón De La Plana, Castellón, Spain

Hospital Universitario Donostia; 🇪🇸 San Sebastián, Gipuzkoa, Spain

Hospital Universitario de Gran Canaria Doctor Negrín; 🇪🇸 Las Palmas De Gran Canaria, Gran Canaria, Spain

Hospital Universitario Principe de Asturias; 🇪🇸 Alcalá de Henares, Madrid, Spain

Hospital Universitario Fundación Alcorcón; 🇪🇸 Alcorcón, Madrid, Spain

HOSPITAL UNIVERSITARIO DE FUENLABRADA (Coordinating Centre); 🇪🇸 Fuenlabrada, Madrid, Spain

Hospital Universitario Infanta Elena; 🇪🇸 Valdemoro, Madrid, Spain

Hospital Universitario Son Espases; 🇪🇸 Palma De Mallorca, Mallorca, Spain

Hospital Universitario Virgen de La Arrixaca; 🇪🇸 El Palmar, Murcia, Spain

Hospital Universitario Torrecárdenas; 🇪🇸 Almería, Spain

Complejo Hospitalario Universitario de Badajoz; 🇪🇸 Badajoz, Spain

Hospital General Universitario de Ciudad Real; 🇪🇸 Ciudad Real, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Md Anderson Cancer Center; 🇪🇸 Madrid, Spain

Hospital Universitario Ramón Y Cajal; 🇪🇸 Madrid, Spain

Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital General Universitario Reina Sofía; 🇪🇸 Murcia, Spain

Hospital Quirónsalud Málaga; 🇪🇸 Málaga, Spain

Hospital Universitario Virgen Del Rocío; 🇪🇸 Sevilla, Spain

Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario Y Politécnico La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Río Hortega; 🇪🇸 Valladolid, Spain

Hospital Clínico Universitario "Lozano Blesa"; 🇪🇸 Zaragoza, Spain