Comparative Study of Mitomycin and Lobaplatin in Advanced Colorectal Cancer Patients With Radical Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy (WUHIPEC02)

Comparative Study on the Efficacy of Mitomycin and Lobaplatin in the Treatment of Advanced Colorectal Cancer Patients With Radical Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy

This study is a prospective, randomized, comparative clinical trial conducted by Wuhan Union Hospital and aim to compare the therapeutic effects of Mitomycin and Lobaplatin in the treatment of advanced colorectal cancer patients with radical surgery combined with hyperthermic intraperitoneal chemotherapy

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Surgery; Metastasis; Chemotherapy Effect; Survival
• Intervention / Treatment: Drug: Mitomycin; Drug: Lobaplatin

Detailed Description

Hyperthermic intraperitoneal chemotherapy (HIPEC) is traditionally used to treat peritoneal cancer combined with cytoreductive surgery (CRS). Further, there have been more than 20 years for CRS + HIPEC applying in treatment of patients with colorectal cancer peritoneal metastasis. While, to date, the kinds, doses, combinations of HIPEC drugs are not clearly been evaluate a criterion for local advanced colorectal cancer patients. Thus, This study aim to compare the efficacy of Mitomycin and Lobaplatin in the treatment of advanced colorectal cancer patients with radical surgery combined with HIPEC. We plan to recruit 201 patients and divide into 3 groups, 2 drug groups and 1 control group, radomly. all patients with advanced co cancer receive radical surgery + HIPEC + mFOLFOX6/XELOX chemotherapy regimen. the mainly experimental variable is HIPEC drugs and three groups employ Mitomycin, Lobaplatin and none respectively. the endpoints of study include peritoneal metastasis, overall survival, immune status and perioperative safety assessment.

• Study Type: Interventional
• Enrollment (Anticipated): 201
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kaixiong Tao, Professor; Phone Number: +86- 027-85351662; Email: kaixiongtao@hust.edu.cn
• Study Contact Backup: Name: Cuanqing Wu, Doctor; Phone Number: +86-13995598966; Email: linyaomt@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. No chemoradiotherapy or other anti-tumor therapy before clinical trial performed;
2. Aged 18-75 years;
3. Male or non-pregnant or lactating women;
4. Pathological diagnosis of colorectal adenocarcinoma;
5. Clinical diagnosis of T3 stage or above without distant metastasis and can be given radical surgery (AJCC Version 8, 2018);
6. Normal function of major organs;

7. Routine blood examinations meeting the following criteria:

   A. HB ≥ 90 g/L; B. ANC ≥ 1.5 x 10 9 /L; C. PLT ≥ 125 × 10 9 /L;

8. Chemistry indexs meeting the following criteria:

   A. TBIL < 1.5ULN; B. ALT and AST < 2.5ULN; ALB > 30 g/L C. serum Cr ≤ 1.25 ULN or endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);

9. ECOG score 0-1;

Exclusion Criteria:

1. A history of other malignant tumors within 5 years;
2. Distant metastasis found during surgery;
3. Allergic to paclitaxel, lobaplatin and other related chemotherapeutic drugs;
4. Suffering from epilepsy or other mental illness, unable to control behavior;
5. Inability to tolerate surgery due to severe cardiac, pulmonary and vascular disease;
6. Pregnant or lactating women.
7. Receiving anti-cancer drug therapy from other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug group 1; hyperthermic intraperitoneal chemotherapy (HIPEC) (with Mitomycin): Temperature Setting : 43 ± 1.0 ℃. Perfusion time: 60 min. Amount of perfusate: The perfusion fluid is based on the principle of filling the abdominal cavity and unobstructed circulation. Choice of perfusate: Normal saline. Drug selection and dose: Mitomycin 30 mg/m2 . Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).	Drug: Mitomycin; Mitomycin is used as drug for hyperthermic intraperitoneal chemotherapy. Choice of perfusate: Normal saline. Drug selection and dose: Mitomycin 30mg/m2. Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).
Experimental: Drug group 2; hyperthermic intraperitoneal chemotherapy (HIPEC) (with lobaplatin): Temperature Setting : 43 ± 1.0 ℃. Perfusion time: 60 min. Amount of perfusate: The perfusion fluid is based on the principle of filling the abdominal cavity and unobstructed circulation. Choice of perfusate: Normal saline. Drug selection and dose: lobaplatin 50 mg/m2 . Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).	Drug: Lobaplatin; Lobaplatin is used as drug for hyperthermic intraperitoneal chemotherapy. Choice of perfusate: Normal saline. Drug selection and dose: Lobaplatin 50mg/m2. Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).
No Intervention: Control group; hyperthermic intraperitoneal therapy (HIPET) (no drug) : Temperature Setting : 43 ± 1.0 ℃. Perfusion time: 60 min. Amount of perfusate: The perfusion fluid is based on the principle of filling the abdominal cavity and unobstructed circulation. Choice of perfusate: Normal saline. Drug selection and dose: no drug. Treatment course: 2 times (the first time is after surgery, the second time is 48h after first time).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
peritoneal metastasis	peritoneal metastasis-free survival (pRFS)	3-year
overall survival	overall survival (OS)	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immunosuppression events as assessed by blood immunological indicators	Before and After Hyperthermic Intraperitoneal Chemotherapy, collect 5mL blood samples of patients for detecting immunological indicators such as CD3, CD4 and CD8 lymphocyte population; Interferon-γ; tumor necrosis factor (TNF)-α; interleukin-2, 4, 8, 10, etc	up to 4 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	postoperative adverse events (referring to CTCAE 5.0 [including blood routine, liver and kidney function, patient reaction to HIPEC, adverse events]) was analyzed	up to 4 weeks
The positive rate of cancer cells of participants by exfoliative cytology examination	According to the positive rate of cancer cells measured in exfoliative cytology before and after HIPEC, the difference between the groups is analyzed.	1 week

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Principal Investigator: Kaixiong Tao, Professor, Wuhan Union Hospital, China

Publications and helpful links

General Publications

• Wisselink DD, Braakhuis LLF, Gallo G, van Grevenstein WMU, van Dieren S, Kok NFM, de Reuver PR, Tanis PJ, de Hingh IHJT. Systematic review of published literature on oxaliplatin and mitomycin C as chemotherapeutic agents for hyperthermic intraperitoneal chemotherapy in patients with peritoneal metastases from colorectal cancer. Crit Rev Oncol Hematol. 2019 Oct;142:119-129. doi: 10.1016/j.critrevonc.2019.06.014. Epub 2019 Jul 9.
• Yan TD, Cao CQ, Munkholm-Larsen S. A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy. World J Gastrointest Oncol. 2010 Feb 15;2(2):109-16. doi: 10.4251/wjgo.v2.i2.109.
• Hompes D, Tiek J, Wolthuis A, Fieuws S, Penninckx F, Van Cutsem E, D'Hoore A. HIPEC in T4a colon cancer: a defendable treatment to improve oncologic outcome? Ann Oncol. 2012 Dec;23(12):3123-3129. doi: 10.1093/annonc/mds173. Epub 2012 Jul 25.
• Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2012 May;99(5):699-705. doi: 10.1002/bjs.8679. Epub 2012 Jan 27.
• Razenberg LG, van Gestel YR, Creemers GJ, Verwaal VJ, Lemmens VE, de Hingh IH. Trends in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of synchronous peritoneal carcinomatosis of colorectal origin in the Netherlands. Eur J Surg Oncol. 2015 Apr;41(4):466-71. doi: 10.1016/j.ejso.2015.01.018. Epub 2015 Jan 29.
• Torphy RJ, Stewart C, Sharma P, Halpern AL, Oase K, Herter W, Bartsch C, Friedman C, Del Chiaro M, Schulick RD, Gleisner A, McCarter MD, Ahrendt SA. Dextrose-Containing Carrier Solution for Hyperthermic Intraperitoneal Chemotherapy: Increased Intraoperative Hyperglycemia and Postoperative Complications. Ann Surg Oncol. 2020 Dec;27(13):4874-4882. doi: 10.1245/s10434-020-08330-y. Epub 2020 Apr 19.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2026

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 9, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: prognosis; hyperthermic intraperitoneal chemotherapy; advanced colorectal cancer; mitomycin; lobaplatin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Body Temperature Changes; Heat Stress Disorders; Colorectal Neoplasms; Hyperthermia; Fever; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: UHCT-IEC-SOP-016-21-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: we would like to share IPD to other researchers 1 years after clinical trial finished
• IPD Sharing Time Frame: we would like to share IPD to other researchers 1 years after clinical trial finished
• IPD Sharing Access Criteria: all data should not been used for commercial purpose and other private purpose and only for academic research
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No