Clinical Trial to Evaluate Safety and Efficacy of Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) With Mitomycin C Used During Surgery for Treatment of Locally Advanced Colorectal Carcinoma (HIPECT4)

Multicentre, Randomized Clinical Trial to Evaluate Safety and Efficacy of Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) With Mitomycin C Used During Surgery for Treatment of Locally Advanced Colorectal Carcinoma

The purpose of this study is to determine whether Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma is effective in the treatment of locally advanced colorectal carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: MITOMYCIN-C 30 mg; Procedure: Proactive cytoreductive surgery

Detailed Description

The purpose of this study is to determine whether Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma is effective in the treatment of locally advanced colorectal carcinoma.

The Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) is expected to be an effective treatment with minimal side effects, it has already provided clear benefits in terms of overall survival in patients with advanced cancer.

This is an attractive option for the healthcare professionals who face daily to peritoneal recurrence after performing complex surgeries, however its application is difficult due to the cost and resources increase. This leads to the necessity of administering the treatment within a clinical trials and in order to obtain a significant power this clinical trials will be multicenter and it will be performed in several Oncological surgery Units highly specialised and with extensive experience in colorectal carcinoma.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Almería, Spain, 04009
    • Hospital Universitario Torrecárdenas
  • Badajoz, Spain, 06080
    • Hospital Universitario de Badajoz
  • Ciudad Real, Spain, 13005
    • Hospital General Universitario De Ciudad Real
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofía
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Díaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28033
    • Md Anderson Cancer Center
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Murcia, Spain, 30003
    • Hospital General Universitario Reina Sofía
  • Málaga, Spain
    • Hospital Regional Universitario de Malaga
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncología
  • Barcelona
    • Sant Joan Despí, Barcelona, Spain, 08970
      • Hospital de Sant Joan Despí. Moisès Broggi
  • Castellón
    • Castellón De La Plana, Castellón, Spain, 12002
      • Hospital Provincial de Castellón
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain
      • Hospital Universitario Son Espases
  • Islas Canarias
    • Las Palmas De Gran Canaria, Islas Canarias, Spain, 35019
      • Hospital Universitario de Gran Canaria "Dr. Negrin"
    • Santa Cruz De Tenerife, Islas Canarias, Spain, 38010
      • Hospital Universitario Nuestra Señora de Candelaria
  • Madrid
    • Alcalá De Henares, Madrid, Spain
      • Hospital Universitario Príncipe de Asturias
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female patients between the ages of 18 and 75 years;
2. Adenocarcinoma of the colon, sigma and colon-sigma joint which represent cT4a/b in line with The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual;
3. Lymph node involvement: N0, the presence of N1/2 according to the 7th edition of the AJCC is allowed, provided that they can be resectable;
4. Metastatic extent: M0;
5. Karnofsky index >70 or Performance status ≤2;
6. Informed consent properly completed.

Exclusion Criteria:

1. Presence of metastases (M1), in case of liver or peritoneal metastases at the time of surgery, the patient will be excluded from the trial and treated according to their new stage.
2. Presence of unresectability criteria;
3. Urgent intervention due to obstruction or perforation if there is tumor removal, prior interventions will be accepted as referrals without primary tumor removal or drainage of collections prior to scheduled surgery.
4. Extraperitoneal rectal cáncer (avoiding alterations for neoadyuvance);
5. Coexistence of another malignant neoplastic disease (synchronous tumors of the colon and upper rectum are accepted as long as the stage is equal to or less than the treated tumor).
6. Severely altered liver, kidney and cardiovascular function;
7. Intolerance to treatment;
8. Administration of chemotherapy before the trial (use of neoadyuvance is discarded);
9. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proactive cytoreductive surgery + HIPEC; Tumoral cytoreductive surgery + apendicectomy + total omentectomy + round hepatic ligament + oophorectomy (postmenopausian women) plus HIPEC (Mytomicin C - 60 minutes).	Drug: MITOMYCIN-C 30 mg; Proactive cytoreductive surgery: Tumoral cytoreductive surgery + apendicectomy + total omentectomy + round hepatic ligament + oophorectomy (postmenopausian women) plus HIPEC with Mytomicin C for 60 minutes.
Active Comparator: Proactive cytoreductive surgery; Tumoral cytoreductive surgery + apendicectomy + total omentectomy + round hepatic ligament + oophorectomy (postmenopausian women).	Procedure: Proactive cytoreductive surgery; Proactive cytoreductive surgery: Tumoral cytoreductive surgery + apendicectomy + total omentectomy + round hepatic ligament + oophorectomy (postmenopausian women)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional Control (LC)	Time elapsed from the surgical intervention clinical up to the date the patient is free of clinical and radiological locoregional recurrence	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Evaluate the effect of the addition of HIPEC with Mitomycin C to cytoreductive surgery in 12 months and 3 years overall survival rate (%OS).	12 months and 36 months after surgery
Disease Free Survival	Evaluate the effect of addition of HIPEC with Mitomycin C to cytoreductive surgery in 12 months and 3 years disease free survival rate (% DFS).	12 months and 36 months after surgery
Evaluation of the morbidity and mortality related with the treatment	Evaluate the safety (treatment-related morbidity and mortality) of addition of HIPEC with Mitomycin C to cytoreductive surgery in locally advanced colo-rectal cancer. It will be measured by the incidence rate of adverse events and deaths.	36 months after surgery
HIPEC technique operating time	Average operating time calculation.	36 months after surgery
HIPEC technique length of hospital stay	Average length of hospital stay calculation.	36 months after surgery
HIPEC technique re-admission rate	Average re-admission rate calculation.	36 months after surgery
HIPEC technique laparoscopic vs laparotomy approach	With this outcome it will be calculated the frequency of both surgery techniques and if it has any impact on the locoregional control of the disease.	36 months after surgery
HIPEC technique open vs. closed HIPEC technique	With this outcome it will be calculated the frequency of both surgery techniques and if it has any impact on the locoregional control of the disease.	36 months after surgery
Quality of life questionnaire QLQ-C30	With this outcome it will be calculated the effect on the quality of life of patients using questionnaire QLQ-C30.	At baseline, 1 month after surgery, 6 months after surgery, 12 months after surgery, 24 months after surgery and 36 months after surgery
Quality of life questionnaires QLQ-CR29	With this outcome it will be calculated the effect on the quality of life of patients using questionnaire QLQ-CR29.	At baseline, 1 month after surgery, 6 months after surgery, 12 months after surgery, 24 months after surgery and 36 months after surgery

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Investigators: Principal Investigator: Álvaro Arjona Sánchez, MD, Hospital Universitario Reina Sofía

Publications and helpful links

General Publications

• Arjona-Sanchez A, Barrios P, Boldo-Roda E, Camps B, Carrasco-Campos J, Concepcion Martin V, Garcia-Fadrique A, Gutierrez-Calvo A, Morales R, Ortega-Perez G, Perez-Viejo E, Prada-Villaverde A, Torres-Melero J, Vicente E, Villarejo-Campos P, Sanchez-Hidalgo JM, Casado-Adam A, Garcia-Martin R, Medina M, Caro T, Villar C, Aranda E, Cano-Osuna MT, Diaz-Lopez C, Torres-Tordera E, Briceno-Delgado FJ, Rufian-Pena S. HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma. BMC Cancer. 2018 Feb 13;18(1):183. doi: 10.1186/s12885-018-4096-0.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2015
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: November 9, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimated): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: HIPEC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: FCO-HIP-2015-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The individual participant data will be available.

Individual parcicipant data that underlie the results reportes in this article, after deidenttification (text, tables, figures and appendices)

The other documents that will be available: study protocol, Statistical Analysis Plan, Informed Consent Form.

The data will be available beginning 9 months and ending 36 months following article publication.

With whom? Researchers who provide a methodologically sound proposal.

For what types of analyses? for individual participant data meta-analysis.

• IPD Sharing Time Frame: The data will be available beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: To obtain the data, a proposal must be sent to uicec@imibic.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR