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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: MITOMYCIN-C 30 mg
* Procedure: Proactive cytoreductive surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the ages of 18 and 75 years; 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; 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; Metastatic extent: M0; Karnofsky index >70 or Performance status ≤2; Informed consent properly completed. Exclusion Criteria: 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. Presence of unresectability criteria; 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. Extraperitoneal rectal cáncer (avoiding alterations for neoadyuvance); 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). Severely altered liver, kidney and cardiovascular function; Intolerance to treatment; Administration of chemotherapy before the trial (use of neoadyuvance is discarded); Pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIPEC