Severe Neutropenia After HIPEC Using Mitomycin-C

August 3, 2023 updated by: Eun Jung Park, Gangnam Severance Hospital

A Phase II Trial to Analyze Clinical and Pharmacological Properties for Severe Neutropenia After Cytoreductive Surgery Followed by Hyperthermic Intraperitoneal Chemotherapy Using Mitomycin-C

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Evaluation parameters

  1. Preoperative period

    • Obtaining informed consent
    • Assessment of baseline clinical characteristics: vital sign, BMI, BSA, ASA classification, ECOG, CBC, CEA level
    • Before 1 day of surgery, assessment of QoR-40 questionnaires

  2. Intra-operative period

    • CRS / HIPEC
    • Assessment for peritoneal cancer index, complete cytoreduction score
    • HIPEC procedures: HIPEC was performed using MMC 35 mg/m2 at 41-43℃ for 90 min. Following the HIPEC triple method, MMC 35 mg/m2 was mixed with 3L of Physioneal PD-2 1.5% peritoneal dialysis solution and administered into the intraperitoneal cavity at 50% of the dose at the beginning of HIPEC, 25% of the dose at 30 min, and 25% of the dose at 60 min.

    • Intraoperative samplings of blood and peritoneal fluids during HIPEC :

      • Blood sampling of 5 ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90, 120 min)
      • Peritoneal fluid sampling of 5 ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90 min)

  3. Postoperative period : Postoperative assessment until the discharge date or postoperative 14th days.

    • Daily assessment before discharge : vital sign, transfusion, neutropenia occurrence, adverse events, hematologic blood test (CBC, absolute neutrophil count (ANC), postoperative complications, use of G-CSF, ICU admission (If severe neutropenia occurs in the postoperative period, the patient assigns in arm I.)
    • CEA level: postoperative 5th day
    • QoR-40 questionnaires: postoperative 4th and 7th days

Study Type

Observational

Enrollment (Actual)

74

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

Description

Inclusion Criteria:

  • 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

Exclusion Criteria

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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

- 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 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

- 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Association between the concentration of intraoperative mitomycin-C absoprtion and severe neutropenia after CRS/HIPEC
Time Frame: 2 weeks after the discharge
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of severe neutropenia
Time Frame: During 2 weeks after CRS/HIPEC
Incidence (rates)
During 2 weeks after CRS/HIPEC
Postoperative complications
Time Frame: During 2 weeks after CRS/HIPEC
Assessment from Clavien-Dindo classification
During 2 weeks after CRS/HIPEC
Patterns of perioperative changes of WBC, Hemoglobin, platelet, lymphocyte, neutrophil counts
Time Frame: During 2 weeks after CRS/HIPEC
Records for serologic tests
During 2 weeks after CRS/HIPEC
Frequency of postoperative uses for G-CSF
Time Frame: During 2 weeks after CRS/HIPEC
Numbers of G-CSF uses
During 2 weeks after CRS/HIPEC
Changes of CEA level
Time Frame: During 2 weeks after CRS/HIPEC
ng/mL
During 2 weeks after CRS/HIPEC
Quality of Life: QoR-40 questionnaire
Time Frame: During 2 weeks after CRS/HIPEC
Answer of questionnarie
During 2 weeks after CRS/HIPEC

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gangnam Severance Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2021

Primary Completion (Actual)

March 20, 2023

Study Completion (Actual)

March 20, 2023

Study Registration Dates

First Submitted

August 18, 2022

First Submitted That Met QC Criteria

August 21, 2022

First Posted (Actual)

August 24, 2022

Study Record Updates

Last Update Posted (Actual)

August 7, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3-2021-0122

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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