Clinical trial NCT06839378: Flura-seq for Evaluating the Effects of Different Hyperthermic Intraperitoneal Chemotherapy Regimens on the Transcriptome of Pseudomyxoma Peritonei
Official title: Fluorouracil-labeled Nascent RNA Technology for Evaluating the Effects of Different Hyperthermic Intraperitoneal Chemotherapy Regimens on the Transcriptome of Pseudomyxoma Peritonei
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pseudomyxoma Peritonei
Keywords: Flura-seq
PMP
HIPEC
Fluorouracil-labeled Nascent RNA Technology
Lead sponsor: Beijing Tsinghua Chang Gung Hospital
Sponsor class: OTHER
Collaborators: name: Tsinghua University
First posted: 2025-02-21
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: 1. Participants:

   ① Diagnosed PMP patients;

   ② Patients can receive CRS+HIPEC treatment.
2. Trial protocol: the patients will be randomly divided into cisplatin group and cisplatin + docetaxel group. Preoperative intravenous bolus injection of 5-FU (400 mg/m2) will be given before CRS+HIPEC treatment. After CRS, the patients will be treated with cisplatin or cisplatin + docetaxel HIPEC, respectively. Cisplatin 120 mg or docetaxel 120 mg + Cisplatin 120 mg will be added to 3,000 ml of saline, heated to 43 ℃, and perfused at a flow rate of 400 ml/min for 60 min.
3. Sample collection: tumor tissue samples (5-10 g) will be collected before and after HIPEC treatment, and will be stored at 80 ℃ for nascent transcriptome sequencing.
4. Sequencing analysis of nascent transcriptome: using high-throughput sequencing technology, the RNA extracted from tumor tissue samples before and after treatment with cisplatin or cisplatin + docetaxel HIPEC will be sequenced by Flura-seq to analyze the changes of newly synthesized transcripts in tumor tissue during HIPEC.
5. Data analysis: the sequencing data will be processed and analyzed by bioinformatics methods. The differentially expressed genes in cisplatin group and cisplatin + docetaxel group will be compared to evaluate the efficacy of different HIPEC regimens on PMP. Functional annotation and pathway analysis of differentially expressed genes will be performed to explore molecular therapeutic targets for PMP-specific RNA.
6. Treatment regimen for poor therapeutic effect: the study will not change the patient's existing HIPEC regimen. If the results show that HIPEC is not effective in treating the patient, it means that the drug is not effective for the patient during subsequent chemotherapy, and the chemotherapy regimen can be adjusted accordingly based on the Flura-seq results.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Changes in Nascent RNA in Tumor Tissues Before and After HIPEC
timeFrame: From enrollment to the end of CRS+HIPEC treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
Study officials:
affiliation: Beijing Tsinghua Changgeng Hospital
name: Yan Li, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
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