Clinical trial NCT05250648: Clinical Trial on HIPEC with Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
Official title: Phase IV Multicentric Clinical Trial to Evaluate the Efficacy of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Mytomicin-C After Complete Surgical Cytoreduction in Patients with Colon Cancer Peritoneal Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Peritoneal Carcinomatosis
Colon Cancer
Keywords: HIPEC
Mitomycin
Colon Neoplasms
Peritoneal metastasis
Lead sponsor: Hospital Universitario de Fuenlabrada
Sponsor class: OTHER
Collaborators: name: Instituto de Investigación Hospital Universitario La Paz
First posted: 2022-02-22
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Recruitment will be carried out at the outpatient clinic, once the indication of CRS ± HIPEC (CC-PM of apparently limited volume without metastasis at other sites) has been established after presenting the case in the Multidisciplinary Tumour Board. Eligible patients need to meet the presurgical inclusion criteria (even though some criteria have to be confirmed during surgery for randomization), and sign the informed consent.

Randomization occurs intraoperatively, once the extension of peritoneal disease is found to be truly limited (PCI ≤ 20) after complete surgical exploration, and only after radical surgery (CCS 0) has been possible. At this time, patients are randomized to receive HIPEC with MMC for 90 minutes (Arm 1), or no HIPEC and therefore surgery is finished (Arm 2).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peritoneal Recurrence Free Survival
timeFrame: 3 years
Secondary outcomes:
measure: Global recurrence at any location (Disease Free Survival)
timeFrame: 3 years
measure: Locoregional and distant recurrence rate (isolated or coincident, with or without simultaneous peritoneal recurrence)
timeFrame: 3 years
measure: Postoperative complications (rate and severity grade)
timeFrame: days 1-90 after surgery
measure: Peritoneal and global recurrence rate according to stratified PCI
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Quality of Life with EORTC validated questionnaire Core 30 (QLQ-C30)
timeFrame: pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months
measure: Quality of Life with EORTC validated questionnaire Colorectal Cancer Module (QLQ-CR29).
timeFrame: pre-surgery, at the end of postoperative SCT (an average 4-6 months), at 12 months and at 24 months
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Sant Joan Despí
country: Spain
facility: Hospital Sant Joan Despi Moises Broggi
state: Barcelona
city: Castelló de la Plana
country: Spain
facility: Hospital General Universitario de Castellón
state: Castellón
city: Castellón De La Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellón
state: Castellón
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
state: Gipuzkoa
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrín
state: Gran Canaria
city: Alcalá de Henares
country: Spain
facility: Hospital Universitario Principe de Asturias
state: Madrid
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Fuenlabrada
country: Spain
facility: HOSPITAL UNIVERSITARIO DE FUENLABRADA (Coordinating Centre)
state: Madrid
city: Valdemoro
country: Spain
facility: Hospital Universitario Infanta Elena
state: Madrid
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Mallorca
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de La Arrixaca
state: Murcia
city: Almería
country: Spain
facility: Hospital Universitario Torrecárdenas
city: Badajoz
country: Spain
facility: Complejo Hospitalario Universitario de Badajoz
city: Ciudad Real
country: Spain
facility: Hospital General Universitario de Ciudad Real
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Md Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Ramón Y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital General Universitario Reina Sofía
city: Málaga
country: Spain
facility: Hospital Quirónsalud Málaga
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocío
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Y Politécnico La Fe
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario "Lozano Blesa"
Study officials:
affiliation: Hospital Universitario de Fuenlabrada, Madrid, Spain
name: Fernando Pereira, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pereira F, Serrano A, Manzanedo I, Perez-Viejo E, Gonzalez-Moreno S, Gonzalez-Bayon L, Arjona-Sanchez A, Torres J, Ramos I, Barrios ME, Cascales P, Morales R, Boldo E, Garcia-Fadrique A, Arteaga X, Gutierrez-Calvo A, Sanchez-Garcia S, Asensio E, Ramirez CP, Artiles M, Vaque J, Parra PA, Villarejo P, Munoz-Casares C, Turienzo E, Calero A, Torrejimeno IJ, Prieto I, Galindo J, Borrego V, Marcello ME, Rihuete C, Carrasco J, Gomez-Quiles L. GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases. BMC Cancer. 2022 May 12;22(1):536. doi: 10.1186/s12885-022-09572-7.