Pseudomyxoma Peritonei
Conditions
Keywords
Flura-seq, PMP, HIPEC, Fluorouracil-labeled Nascent RNA Technology
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.
Interventions
PROCEDUREintravenously inject with 5-FU (400 mg/m2)
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.
Sponsors
Tsinghua University
Beijing Tsinghua Chang Gung Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in RNA in Tumor Tissues Before and After HIPEC | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | This secondary outcome quantifies and compares differentially expressed genes (DEGs) identified via Flura-seq (spatial transcriptomics) and bulk RNA-seq methodologies across all samples collected before and after hyperthermic intraperitoneal chemotherapy (HIPEC). |
Countries
China
Participant flow
Recruitment details
Recruitment was conducted at a single-center hospital (Beijing Tsinghua Changgung Hospital, Department of Peritoneal Oncology) from February 17, 2025, to August 6, 2025. Potential participants were identified through outpatient clinics and physician referrals. All screened individuals underwent preliminary eligibility assessment based on the study's inclusion and exclusion criteria.
Pre-assignment details
After providing informed consent, 36 enrolled participants entered a screening phase to confirm eligibility based on predefined inclusion/exclusion criteria. All 36 participants successfully completed screening and proceeded to randomization. No participants were excluded or withdrew during this phase. Using a randomization table provided by the Beijing Tsinghua Changgung Hospital Clinical Data Management Center, the 36 participants were randomly assigned to two groups (18 participants per group
Participants by arm
| Arm | Count |
|---|---|
| Experimental : Cisplatin Group 5-FU (400 mg/m²) has been injected IV bolus before operation. After CRS, the patients have been treated with cisplatin or cisplatin + docetaxel HIPEC respectively. The tumor tissue samples of patients have been collected before and after HIPEC treatment. The tumor tissue samples before and after HIPEC treatment have been sequenced by Flura-seq using high-throughput sequencing technology, and the changes of newly generated transcripts in tumor tissue during HIPEC have been analyzed. The differentially expressed genes in the cisplatin group and the cisplatin + docetaxel group have been compared to evaluate the effect of different HIPEC regimens on the transient transcriptome of PMP tumor. | 18 |
| Active Comparator : Cisplatin + Docetaxel Group 5-FU (400 mg/m²) has been injected IV bolus before operation. After CRS, the patients have been treated with cisplatin or cisplatin + docetaxel HIPEC respectively. The tumor tissue samples of patients have been collected before and after HIPEC treatment. The tumor tissue samples before and after HIPEC treatment have been sequenced by Flura-seq using high-throughput sequencing technology, and the changes of newly generated transcripts in tumor tissue during HIPEC have been analyzed. The differentially expressed genes in the cisplatin group and the cisplatin + docetaxel group have been compared to evaluate the effect of different HIPEC regimens on the transient transcriptome of PMP tumor. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | Total | Active Comparator : Cisplatin + Docetaxel Group | Experimental : Cisplatin Group |
|---|---|---|---|
| Age, Customized Age 18-75 years old | 36 Participants | 18 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 18 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Histological characteristics of 36 PMP patients treated with CRS+HIPEC Acellular mucus | 1 Participants | 1 Participants | 0 Participants |
| Histological characteristics of 36 PMP patients treated with CRS+HIPEC high-grade mucinous carcinoma peritoneum | 10 Participants | 5 Participants | 5 Participants |
| Histological characteristics of 36 PMP patients treated with CRS+HIPEC high-grade mucinous carcinoma peritoneum with sign | 3 Participants | 0 Participants | 3 Participants |
| Histological characteristics of 36 PMP patients treated with CRS+HIPEC low-grade mucinous carcinoma peritoneum | 22 Participants | 12 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 18 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 19 Participants | 10 Participants | 9 Participants |
| Sex: Female, Male Male | 17 Participants | 8 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental : Cisplatin Group | Changes in RNA in Tumor Tissues Before and After HIPEC | 1413 Numbers of changed RNA | Standard Deviation 876 |
| Active Comparator : Cisplatin + Docetaxel Group | Changes in RNA in Tumor Tissues Before and After HIPEC | 1927 Numbers of changed RNA | Standard Deviation 992 |
Secondary
Comparison of Transcriptomic Changes Detected by Flura-seq vs. Bulk RNA-seq
This secondary outcome quantifies and compares differentially expressed genes (DEGs) identified via Flura-seq (spatial transcriptomics) and bulk RNA-seq methodologies across all samples collected before and after hyperthermic intraperitoneal chemotherapy (HIPEC).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental : Cisplatin Group | Comparison of Transcriptomic Changes Detected by Flura-seq vs. Bulk RNA-seq | 1,690 Numbers of changed RNA | Standard Deviation 940 |
| Active Comparator : Cisplatin + Docetaxel Group | Comparison of Transcriptomic Changes Detected by Flura-seq vs. Bulk RNA-seq | 340 Numbers of changed RNA | Standard Deviation 300 |