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CompletedNCT05513183Updated Aug 7, 2023

Severe Neutropenia After HIPEC Using Mitomycin-C

An observational study in Colorectal Cancer Metastatic, Cancer Metastatic to the Peritoneal Cavity and Appendiceal Neoplasm, sponsored by Gangnam Severance Hospital. Completed at 1 site in South Korea. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2023-08-07.

Sponsored by Gangnam Severance Hospital · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
74
Ages
20 Years and older
Sex
All
01

Study 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.

Read the 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
02

Conditions studied

  • Colorectal Cancer Metastatic
  • Cancer Metastatic to the Peritoneal Cavity
  • Appendiceal Neoplasm
  • Pseudomyxoma Peritonei
03

In context

Appendiceal Neoplasms

58 studies on the registry are indexed under Appendiceal Neoplasms; 24 are open to participants now.

This study's enrollment of 74 is below the median of 339 across 16 observational studies indexed under Appendiceal Neoplasms.

Browse Appendiceal Neoplasms studies →

Lead sponsor

Gangnam Severance Hospital is the lead sponsor of 145 studies on the registry; 37 are open to participants now.

Browse Gangnam Severance Hospital studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years and older
Sexes eligible
All
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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
74 participants (actual)
Patient registry
No
Biospecimen retention
Samples without dna

Groups and cohorts

  • 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

  • ProcedureIntraoperative 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)

06

What researchers measure

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

    Time frame: 2 weeks after the discharge

Secondary outcomes

  1. Incidence of severe neutropenia

    Incidence (rates)

    Time frame: During 2 weeks after CRS/HIPEC

  2. Postoperative complications

    Assessment from Clavien-Dindo classification

    Time frame: During 2 weeks after CRS/HIPEC

  3. Patterns of perioperative changes of WBC, Hemoglobin, platelet, lymphocyte, neutrophil counts

    Records for serologic tests

    Time frame: During 2 weeks after CRS/HIPEC

  4. Frequency of postoperative uses for G-CSF

    Numbers of G-CSF uses

    Time frame: During 2 weeks after CRS/HIPEC

  5. Changes of CEA level

    ng/mL

    Time frame: During 2 weeks after CRS/HIPEC

  6. Quality of Life: QoR-40 questionnaire

    Answer of questionnarie

    Time frame: During 2 weeks after CRS/HIPEC

07

Study locations

1 site
  • Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
    Seoul, South Korea
08

References and documents

Publications

  • 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. PubMed 14551293 ↗
  • 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. PubMed 14567024 ↗
  • 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. PubMed 7815285 ↗
  • 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. PubMed 19475451 ↗
  • 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. PubMed 29027153 ↗
  • 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. PubMed 34689262 ↗
  • 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. PubMed 34665362 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from May 2021 to primary completion in Mar 2023, 22 months.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 18, 2022
First posted
Aug 24, 2022
StartActual
May 20, 2021
Primary completionActual
Mar 20, 2023
CompletionActual
Mar 20, 2023
Last update
Aug 7, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 7, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05513183
Lead sponsor
Gangnam Severance Hospital
Responsible party
Eun Jung Park (Assistant Professor, Gangnam Severance Hospital) — Principal investigator
First posted
Aug 24, 2022
Start date
May 20, 2021
Primary completion
Mar 20, 2023
Completion
Mar 20, 2023
Last update
Aug 7, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.

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