Severe Neutropenia After HIPEC Using Mitomycin-C

NCT05513183 | Completed

• 1 other identifier: 3-2021-0122
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) to treat colorectal cancer patients with peritoneal metastases. However, MMC has a side effect of myelosuppression. Particularly, severe neutropenia after CRS with HIPEC can be a life-threatening condition. Despite the postoperative risks of this side effect, the causes and risk factors for severe neutropenia after CRS followed by HIPEC is not identified so far. Therefore, in this study, we aimed to evaluate to evaluate clinical risk factors and pharmacologic properties after CRS with HIPEC using MMC in patients with colorectal cancer or appendiceal mucinous neoplasms with peritoneal metastases.

Conditions

Colorectal Cancer Metastatic; Cancer Metastatic to the Peritoneal Cavity; Appendiceal Neoplasm; Pseudomyxoma Peritonei

Outcome Measures

Primary Outcomes (1)

• Association between the concentration of intraoperative mitomycin-C absoprtion and severe neutropenia after CRS/HIPEC

  Comparison of the pharmacologic association between occurrence of postoperative severe neutropenia, and blood absoprtion rates of MMC and the area-under-the curve (AUC) ratios during HIPEC

  2 weeks after the discharge

Secondary Outcomes (6)

• Incidence of severe neutropenia

  During 2 weeks after CRS/HIPEC

• Postoperative complications

  During 2 weeks after CRS/HIPEC

• Patterns of perioperative changes of WBC, Hemoglobin, platelet, lymphocyte, neutrophil counts

  During 2 weeks after CRS/HIPEC

• Frequency of postoperative uses for G-CSF

  During 2 weeks after CRS/HIPEC

• Changes of CEA level

  During 2 weeks after CRS/HIPEC

Study Arms (2)

Arm I (Severe neutropnia group),

After CRS followed by HIPEC using MMC of 35mg/m2, patients who had absolute neutrophil count (ANC) \< 1000/mm3 during the postoperative period are assigned as experimental group (Arm I, severe neutropnia group).

Procedure: Intraoperative blood and peritoneal fluid samplings during HIPEC

Arm II (No severe neutropenia group)

After CRS followed by HIPEC using MMC of 35mg/m2, patients who had ANC ≥ 1000/mm3 during the postoperative period are assigned as the control group (Arm II: no severe neutropenia group).

Procedure: Intraoperative blood and peritoneal fluid samplings during HIPEC

Interventions

Intraoperative blood and peritoneal fluid samplings during HIPEC PROCEDURE

\- Intraoperative samplings of blood and peritoneal fluids during HIPEC : * Blood sampling of 5ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90, 120 min) * Peritoneal fluid sampline of 5ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90 min)

Arm I (Severe neutropnia group),; Arm II (No severe neutropenia group)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who diagnosed colorectal or appendiceal neoplasms with peritoneal metastases who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using mitomycin-C

You may qualify if:

• Joined the study voluntarily and signed informed consent form
• Patients who diagnosed colorectal cancer or appendiceal mucinous neoplasm with peritoneal metastases
• Patients who undergo CRS/HIPEC using MMC
• ECOG ≤ 1

You may not qualify if:

• Patients who received synchronous operations for liver or lung metastatic sites during CRS/HIPEC
• Previous histories who underwent CRS/HIPEC
• Patients who received palliative 3rd line chemotherapy
• Patients who received chemotherapy within 1 year to treat other cancers
• Patients who had PCD cathethers for ascites control
• ECOG ≥2
• Infectious status
• Age\<19 years old
• Pregnant or breast-feeding women or people during the birth-period who refused to take contraceptives
• Drop-out criteria
• \- Hospital stay \> 30 days

Sponsors & Collaborators

• Gangnam Severance Hospital: lead

Study Sites (1)

Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

Seoul, South Korea

Location

Related Publications (7)

• Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003 Oct 15;21(20):3737-43. doi: 10.1200/JCO.2003.04.187.

  PMID: 14551293 BACKGROUND

• Katz MH, Barone RM. The rationale of perioperative intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies. Surg Oncol Clin N Am. 2003 Jul;12(3):673-88. doi: 10.1016/s1055-3207(03)00034-6.

  PMID: 14567024 BACKGROUND

• Kuzuya T, Yamauchi M, Ito A, Hasegawa M, Hasegawa T, Nabeshima T. Pharmacokinetic characteristics of 5-fluorouracil and mitomycin C in intraperitoneal chemotherapy. J Pharm Pharmacol. 1994 Aug;46(8):685-9. doi: 10.1111/j.2042-7158.1994.tb03883.x.

  PMID: 7815285 BACKGROUND

• Lambert LA, Armstrong TS, Lee JJ, Liu S, Katz MH, Eng C, Wolff RA, Tortorice ML, Tansey P, Gonzalez-Moreno S, Lambert DH, Mansfield PF. Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. Ann Surg Oncol. 2009 Aug;16(8):2181-7. doi: 10.1245/s10434-009-0523-4. Epub 2009 May 28.

  PMID: 19475451 BACKGROUND

• Feferman Y, Bhagwandin S, Kim J, Aycart SN, Feingold D, Labow DM, Sarpel U. Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C. Ann Surg Oncol. 2017 Dec;24(13):3831-3836. doi: 10.1245/s10434-017-6112-z. Epub 2017 Oct 12.

  PMID: 29027153 BACKGROUND

• Park EJ, Lee SJ, Baik SH. ASO Author Reflections: Delayed Occurrence and Postoperative Risks of Mitomycin-C-Induced Neutropenia After Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol. 2022 Mar;29(3):2087-2088. doi: 10.1245/s10434-021-11000-2. Epub 2021 Oct 23. No abstract available.

  PMID: 34689262 BACKGROUND

• Lee SJ, Jeon Y, Lee HW, Kang J, Baik SH, Park EJ. Impact of Mitomycin-C-Induced Neutropenia after Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery in Colorectal Cancer Patients with Peritoneal Carcinomatosis. Ann Surg Oncol. 2022 Mar;29(3):2077-2086. doi: 10.1245/s10434-021-10924-z. Epub 2021 Oct 19.

  PMID: 34665362 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peritoneal fluid and plasma

MeSH Terms

Conditions

Appendiceal Neoplasms; Pseudomyxoma Peritonei

Condition Hierarchy (Ancestors)

Cecal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Cecal Diseases; Intestinal Diseases; Adenocarcinoma, Mucinous; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Cystic, Mucinous, and Serous

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 18, 2022
• First Posted: August 24, 2022
• Study Start: May 20, 2021
• Primary Completion: March 20, 2023
• Study Completion: March 20, 2023
• Last Updated: August 7, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)