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

Phase 2

Not yet recruiting

• Conditions: Colorectal Cancer; Survival; Chemotherapy Effect; Surgery; Metastasis
• Interventions: Drug: Lobaplatin; Drug: Mitomycin

• Registration Number: NCT04845490
• Lead Sponsor: Wuhan Union Hospital, China

Brief Summary

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

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 Timeline

• Status Verified: 2021-04
• Study First Submitted: 2021-04-06
• Study First Submitted QC: 2021-04-09
• Study First Posted: 2021-04-15
• Last Update Submitted: 2022-02-18
• Last Update Posted: 2022-02-21
• Study Start: 2022-09-01
• Primary Completion: 2023-09-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 201

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Drug group 2	Lobaplatin	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 group 1	Mitomycin	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).

Primary Outcome Measures

Name	Time	Method
peritoneal metastasis	3-year	peritoneal metastasis-free survival (pRFS)
overall survival	3-year	overall survival (OS)

Secondary Outcome Measures

Name	Time	Method
Number of participants with immunosuppression events as assessed by blood immunological indicators	up to 4 weeks	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
The positive rate of cancer cells of participants by exfoliative cytology examination	1 week	According to the positive rate of cancer cells measured in exfoliative cytology before and after HIPEC, the difference between the groups is analyzed.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	up to 4 weeks	postoperative adverse events (referring to CTCAE 5.0 \[including blood routine, liver and kidney function, patient reaction to HIPEC, adverse events\]) was analyzed