Flura-seq for Evaluating the Effects of Different Hyperthermic Intraperitoneal Chemotherapy Regimens on the Transcriptome of Pseudomyxoma Peritonei

NCT06839378 | Completed Results DMC

• 1 other identifier: 24753-0-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to combine HIPEC regimens with Flura-seq to detect the effects of different HIPEC regimens (cisplatin vs. cisplatin+ docetaxel) on the nascent transcriptome of PMP tumors, so as to quantitatively assess the efficacy of different HIPEC regimens in the early stage, and to lay the foundation for optimizing the HIPEC regimens and exploring new therapeutic targets.

Conditions

Pseudomyxoma Peritonei

Keywords

Flura-seq; PMP; HIPEC; Fluorouracil-labeled Nascent RNA Technology

Outcome Measures

Primary Outcomes (1)

• Changes in RNA in Tumor Tissues Before and After HIPEC

  Main index parameters: information on the amount of differentially expressed genes and the magnitude of change between the cisplatin group and the cisplatin+ docetaxel group. The amount of differentially expressed genes is expressed as mean ± standard deviation and statistically analyzed by t-test or rank-sum test, and the comparison between groups is performed by unpaired t-test. Differences are considered statistically significant when P\< 0.05. Based on the statistical results, the efficacy of the two HIPEC regimens (cisplatin or cisplatin+ docetaxel) on PMP will be analyzed. Expected results and clinical interpretation: More changes in newly generated RNA in the tumor tissue indicate a greater impact of HIPEC on the transcriptome of the tumor cells, possibly indicating better efficacy.

  From the initiation of Cytoreductive Surgery (CRS) to the completion of Hyperthermic Intraperitoneal Chemotherapy (HIPEC). CRS takes 4-8 hours, HIPEC takes 1 hour. Pre and post-HIPEC tumor tissues were collected for RNA-sequencing.

Secondary Outcomes (1)

• Comparison of Transcriptomic Changes Detected by Flura-seq vs. Bulk RNA-seq

  From the initiation of Cytoreductive Surgery (CRS) to the completion of Hyperthermic Intraperitoneal Chemotherapy (HIPEC). CRS takes 4-8 hours, HIPEC takes 1 hour. Pre and post-HIPEC tumor tissues were collected for RNA-sequencing.

Study Arms (2)

Cisplatin Group

EXPERIMENTAL

After completing CRS, the patient will undergo cisplatin HIPEC treatment. Add 120 mg of cisplatin to 3000 ml of physiological saline, heat to 43 ℃, perfuse at a flow rate of 400 ml/min, and perfuse for 60 minutes.

Procedure: intravenously inject with 5-FU (400 mg/m2)

Cisplatin + Docetaxel Group

ACTIVE COMPARATOR

After completing CRS, the patient will undergo HIPEC treatment with cisplatin and docetaxel. Add 120 mg of docetaxel and 120 mg of cisplatin to 3000 ml of physiological saline, heat to 43 ℃, perfuse at a flow rate of 400 ml/min, and perfuse for 60 minutes.

Procedure: intravenously inject with 5-FU (400 mg/m2)

Interventions

intravenously inject with 5-FU (400 mg/m2) PROCEDURE

5-FU (400 mg/m2) will be injected IV bolus before operation. After CRS, the patients will be treated with cisplatin or cisplatin + docetaxel HIPEC respectively. The tumor tissue samples of patients will be collected before and after HIPEC treatment. The tumor tissue samples before and after HIPEC treatment will be sequenced by Flura-seq using high-throughput sequencing technology, and the changes of newly generated transcripts in tumor tissue during HIPEC will be analyzed. The differentially expressed genes in the cisplatin group and the cisplatin + docetaxel group will be compared to evaluate the effect of different HIPEC regimens on the transient transcriptome of PMP tumor.

Cisplatin + Docetaxel Group; Cisplatin Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years old, regardless of gender and race;
• Pathologically confirmed as pseudomyxoma peritonei; acceptable for CRS+HIPEC treatment;
• KPS score ≥ 60, with expected survival time more than 12 months;
• The functions of important organs are basically normal, with no significant abnormalities in liver or kidney function;
• No history of allergy to biological products;
• No serious bacterial or viral infection;
• Non-pregnancy and lactation;
• The patient or his/her delegate understands and cooperates with the treatment and signs the informed consent for the treatment.

You may not qualify if:

• Highly allergic or with a history of severe allergies, especially to biological products;
• Shock, systemic failure, unstable vital signs, and inability to cooperate with the examination;
• Those who have mental or psychological diseases and cannot cooperate with treatment and curative effect evaluation;
• T-lymphocyte carcinoma/tumor;
• Patients with systemic infection or severe local infection requiring anti-infection treatment;
• Complicated with dysfunction of heart, lung, brain, kidney, liver and other important organs;
• Coagulation disorders (e.g., hemophilia);
• Infectious diseases (e.g. HIV, RPR, active TB, etc.);
• Pregnant or lactating women, or women who have pregnancy plans within half a year;
• Patients who are taking immunosuppressive drugs or long-term anti-rejection drugs after organ transplantation;
• Patients with severe autoimmune diseases;
• Any life-threatening disease, physical condition or organ system dysfunction that the researcher believes may damage the safety of subjects and expose the research results to unnecessary risks; Drug-dependent persons;
• Patients and/or authorized family members who refuse or do not actively sign the informed consent;
• Participants in other clinical studies within 3 months.

Sponsors & Collaborators

• Beijing Tsinghua Chang Gung Hospital: lead
• Tsinghua University: collaborator

Study Sites (1)

Beijing Tsinghua Changgung Hospital

Beijing, China

Location

Related Publications (9)

• Wang Q, Lu F, Lan R. RNA-sequencing dissects the transcriptome of polyploid cancer cells that are resistant to combined treatments of cisplatin with paclitaxel and docetaxel. Mol Biosyst. 2017 Sep 26;13(10):2125-2134. doi: 10.1039/c7mb00334j.

  PMID: 28825433 BACKGROUND

• Mehta AM, Huitema AD, Burger JW, Brandt-Kerkhof AR, van den Heuvel SF, Verwaal VJ. Standard Clinical Protocol for Bidirectional Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Systemic Leucovorin, 5-Fluorouracil, and Heated Intraperitoneal Oxaliplatin in a Chloride-Containing Carrier Solution. Ann Surg Oncol. 2017 Apr;24(4):990-997. doi: 10.1245/s10434-016-5665-6. Epub 2016 Nov 28.

  PMID: 27896510 BACKGROUND

• Basnet H, Tian L, Ganesh K, Huang YH, Macalinao DG, Brogi E, Finley LW, Massague J. Flura-seq identifies organ-specific metabolic adaptations during early metastatic colonization. Elife. 2019 Mar 26;8:e43627. doi: 10.7554/eLife.43627.

  PMID: 30912515 BACKGROUND

• Fernandez RN, Daly JM. Pseudomyxoma peritonei. Arch Surg. 1980 Apr;115(4):409-14. doi: 10.1001/archsurg.1980.01380040037006.

  PMID: 7362446 BACKGROUND

• Chua TC, Moran BJ, Sugarbaker PH, Levine EA, Glehen O, Gilly FN, Baratti D, Deraco M, Elias D, Sardi A, Liauw W, Yan TD, Barrios P, Gomez Portilla A, de Hingh IH, Ceelen WP, Pelz JO, Piso P, Gonzalez-Moreno S, Van Der Speeten K, Morris DL. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012 Jul 10;30(20):2449-56. doi: 10.1200/JCO.2011.39.7166. Epub 2012 May 21.

  PMID: 22614976 BACKGROUND

• Hinson FL, Ambrose NS. Pseudomyxoma peritonei. Br J Surg. 1998 Oct;85(10):1332-9. doi: 10.1046/j.1365-2168.1998.00882.x.

  PMID: 9782010 BACKGROUND

• Carr NJ, Cecil TD, Mohamed F, Sobin LH, Sugarbaker PH, Gonzalez-Moreno S, Taflampas P, Chapman S, Moran BJ; Peritoneal Surface Oncology Group International. A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process. Am J Surg Pathol. 2016 Jan;40(1):14-26. doi: 10.1097/PAS.0000000000000535.

  PMID: 26492181 BACKGROUND

• Ramaswamy V. Pathology of Mucinous Appendiceal Tumors and Pseudomyxoma Peritonei. Indian J Surg Oncol. 2016 Jun;7(2):258-67. doi: 10.1007/s13193-016-0516-2. Epub 2016 Mar 19.

  PMID: 27065718 BACKGROUND

• Smeenk RM, Bruin SC, van Velthuysen ML, Verwaal VJ. Pseudomyxoma peritonei. Curr Probl Surg. 2008 Aug;45(8):527-75. doi: 10.1067/j.cpsurg.2008.04.003. No abstract available.

  PMID: 18590843 BACKGROUND

MeSH Terms

Conditions

Pseudomyxoma Peritonei

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Adenocarcinoma, Mucinous; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The case number is limited as PMP is a rare disease. Conducting future multicenter studies could potentially facilitate the accumulation of a larger sample size, thereby enabling more robust analyses.

Results Point of Contact

• Title: Yan Li, Director of the Department of Peritoneal Oncology
• Organization: Tsinghua Changgung Hospital

lya03816@btch.edu.cn

+86 18612709123

Study Officials

• Yan Li, PhD

  Beijing Tsinghua Changgeng Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Surgical Oncology

Model Details: This study is a single-center, double-arm, open-label exploratory clinical study. The patients will be randomly divided into cisplatin group and cisplatin + docetaxel group, each group contains 18 patients. 5-FU (400 mg/m2) will be injected IV bolus before operation. After CRS, the patients will be treated with cisplatin or cisplatin + docetaxel HIPEC respectively. The tumor tissue samples of patients will be collected before and after HIPEC treatment. The tumor tissue samples before and after HIPEC treatment will be sequenced by Flura-seq using high-throughput sequencing technology, and the changes of newly generated transcripts in tumor tissue during HIPEC will be analyzed. The differentially expressed genes in the cisplatin group and the cisplatin + docetaxel group will be compared to evaluate the effect of different HIPEC regimens on the transient transcriptome of PMP tumor. It lays a foundation for optimizing HIPEC regimen and judging new therapeutic targets.

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: February 21, 2025
• Study Start: February 17, 2025
• Primary Completion: August 6, 2025
• Study Completion: October 30, 2025
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From 2025 to 2028
• Access Criteria: For information sharing, contact the PI to access the IPD

Locations

CN (1)