Peritoneal MesotheliomaPhase 1NCT04847063
Individual Response to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Histologies
A Phase 1 study testing Sodium Thiosulfate, 5-Fluorouracil and Oxaliplatin in people with Peritoneal Mesothelioma and Peritoneal Carcinomatosis, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is hyperthermic (heated) chemotherapy that washes the inside of the abdomen. CRS with HIPEC may help people with peritoneal carcinomatosis. These are tumors that have spread to the lining of the abdomen from other cancers. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Peritoneal Mesothelioma, Peritoneal Carcinomatosis, Ovarian Cancer
- What is being tested?
- Sodium Thiosulfate, 5-Fluorouracil and Oxaliplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2021to 30 Dec 2034
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmation of peritoneal carcinomatosis from peritoneal mesothelioma or atypical mesothelial proliferation, or from appendiceal, colorectal, or ovarian, histologies by the Laboratory of Pathology, NCI.
- Measurable or evaluable disease as defined by RECIST v1.1. criteria and/or by peritoneal carcinomatosis index (PCI) score.
- Participants must be assessed to be able to undergo optimal cytoreduction (i.e., completeness of cytoreduction score of 1 or 0) with laparoscopically assessed PCI score threshold as indicated below:
- Primary Histology: Appendiceal/Colorectal/Ovarian / PCI Cutoff for Eligibility: Total Score < 20 (out of 39 possible points)
- Primary Histology: Mesothelioma or atypical mesothelial proliferation / PCI Cutoff for Eligibility: Total Score <= 30 (out of 39 possible points)
- Age >= 18 years.
Show all 18Show fewer
- ECOG performance status <= 1 (Karnofsky >= 80%).
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 75,000/mcL
- Total bilirubin within <=1.5x institutional upper limit of normal (ULN)
- AST (SGOT)/ ALT (SGPT) <= 3x institutional upper limit of normal (ULN), or <= 5.0x ULN in participants with liver metastases (only)
- Creatinine within normal institutional limits
- OR
- --Creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal calculated using eGFR.
- Because therapeutic agents used in this trial are known to be teratogenic, individuals of child-bearing potential (IOCBP) and individuals who are able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 180 days after last study treatment.
- Ability of participant to understand and the willingness to sign a written informed consent document.
- Ability and willingness of the participant to co-enroll on the tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors .
Who cannot join
- Participants with known extra-abdominal metastatic disease from the participant s appendiceal, colorectal, ovarian, or peritoneal mesothelioma primary.
- Participants who have received intraperitoneal chemotherapy or other anti-cancer therapy within the last 4 weeks prior to the start of study treatment.
- Participants who have undergone major surgery within the last 12 weeks prior to the start of study treatment.
- History of allergic reactions attributed to platinum-containing compounds.
- History of dihydropyrimidine dehydrogenase deficiency (only participants with appendiceal or colorectal cancer).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant individuals are excluded from this study because the protocol involves major abdominal surgery and chemotherapeutic agents with the potential for teratogenic or abortifacient effects. Note: Due to an unknown but potential risk for adverse events in nursing infants secondary to treatment of the participant, nursing (including breastfeeding) should be discontinued if the participant is undergoing treatment (i.e., nursing participants must agree to discontinue nursing activities).
- HIV-positive participants with detectable viral load despite antiretroviral therapy are ineligible because of participants increased risk of lethal infections when treated with marrow-suppressive therapy. HIV-positive participants who have undetectable viral load on antiretroviral therapy may be considered for this study only after consultation with a NIAID physician.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937
About this study
Official title: Individualized Response Assessment to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Primaries
Background:
Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is hyperthermic (heated) chemotherapy that washes the inside of the abdomen. CRS with HIPEC may help people with peritoneal carcinomatosis. These are tumors that have spread to the lining of the abdomen from other cancers. Researchers think they can improve the results of CRS with HIPEC treatment on these tumors by choosing the chemotherapy drugs used in HIPEC.
Read more
Objective:
To see if HIPEC after CRS can be improved, using either a model called the SMART (Sustained Microenvironment for Analysis of Resected Tissue) System or using 3-D cell culture (organoid) models, in order to test different chemotherapy drugs on tumors that were surgically removed prior to HIPEC treatment (these models are not attached to the body) versus tumors that were treated with HIPEC while still inside the body before being immediately surgically removed.
Eligibility:
Adults ages 18 and older who have peritoneal carcinomatosis that cannot be fully removed safely with surgery.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Electrocardiogram (EKG)
Computed tomography (CT) scan
Other imaging scans, as needed
Tumor biopsy, if needed
Laparoscopy (small cuts are made in the abdomen, and a tube with a light and a camera is used to see the organs in the abdomen), if needed
Participants will enroll in NIH protocol #13C0176. This allows their tumor samples to be used in future research.
Some screening tests may be repeated in the study.
Participants will have CRS. As many of their visible tumors will be removed as possible during surgery except for a few specific tumors left to receive the HIPEC treatment. Then they will receive HIPEC and the remaining tumors will be immediately removed. Participants will be in the hospital for 7-21 days after this surgery (CRS with HIPEC).
Participants will give tumor, fluid samples (from the abdomen during surgery), blood, saliva, cheek swab, and stool for research. They will complete surveys about their health and quality of life.
Participants with peritoneal mesothelioma (mesothelioma primary only) will have genetic (DNA) testing to determine clinical (CLIA level) germline BAP1 status for research use.
Participants will have follow-up visits for up to 5 years from CRS with HIPEC.
If there is disease progression, participants may have CRS with HIPEC again. Participants will then have follow-up visits for up to 5 years from the date of last CRS with HIPEC.
...
Read the detailed description
Background:
Peritoneal carcinomatosis is uniformly fatal if untreated; improved outcomes are seen with aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
The selection of chemotherapeutic agent for HIPEC is largely based on primary tumor histology and provider preference as opposed to knowledge of the potential efficacy of a specific agent for an individual patient.
HIPEC is intended to target small or microscopic residual disease following complete cytoreduction; however, the actual efficacy and additional benefit of HIPEC is in question.
Tissue response to simulated ex vivo HIPEC treatment in the SMART System or 3-D cell culture (organoid) models could inform chemotherapeutic agent selection for subsequent cytoreduction and intra-operative in vivo HIPEC treatments.
Objective:
To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67
Eligibility:
Histologically confirmed peritoneal carcinomatosis from peritoneal mesothelioma or atypical mesothelial proliferation, or from appendiceal, colorectal, or ovarian, histologies
Absence of extra-abdominal metastatic disease
Participant deemed able to undergo optimal cytoreduction
Age >= 18 years of age
Design:
This is a Phase I study of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with randomization to one of two accepted HIPEC treatment regimens as determined by primary histology.
At the time of cytoreduction, representative peritoneal tumor biopsies will be obtained before and after intra-operative in vivo HIPEC treatment.
Tumor nodules harvested before intra-operative HIPEC will be placed in either the SMART System or 3-D cell culture (organoid) models, exposed to simulated ex vivo HIPEC treatment, and then perfused or maintained in culture, with subsequent assessment
of percent necrosis and Ki-67.
Tumor nodules harvested immediately after intra-operative HIPEC will be placed in the SMART System or 3-D cell culture (organoid) models and perfused or maintained in culture, with subsequent assessment of percent necrosis and Ki-67.
The correlation of percent necrosis and Ki-67 assessment following simulated ex vivo HIPEC and intra-operative in vivo HIPEC will be determined.
- Conditions
- Peritoneal Mesothelioma, Peritoneal Carcinomatosis, Ovarian Cancer, Gastrointestinal Cancer, Appendiceal Cancer, Atypical Mesothelial Proliferation
- Being tested
- Sodium Thiosulfate, 5-Fluorouracil, Oxaliplatin, Doxorubicin, Hyperthermic Intraperitonial Chemotherapy
- Keywords
- cytoreduction, organoid model, cell culture model, SMART System, Peritoneal Metastasis, necrosis, Ki-67, cytoreductive surgery (CRS)
- Medical subject headings
- Peritoneal Neoplasms, Ovarian Neoplasms, Gastrointestinal Neoplasms, Appendiceal Neoplasms, Colorectal Neoplasms, Necrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium ThiosulfateDrug
Part of Arms 3 and 4, for cisplatin-based HIPEC: intravenous sodium thiosulfate given as a loading dose of 7.5 g/m2 in 150 mL 0.9% sodium chloride at the time of introducing cisplatin into the perfusion circuit, followed by a 12-hour pump-based infusion of 25.56 g/m2 in 1 L 0.9% sodium chloride
5-FluorouracilDrug
Part of Arm 1, for oxaliplatin-based HIPEC: intravenous 5-fluorouracil given at a dose of 400 mg/m2 in 250 mL 0.9% sodium chloride over 10 minutes, co-administered with intravenous leucovorin at 20 mg/m2 in a separate bag of 250 mL 0.9% sodium chloride
OxaliplatinDrug
Arm 1, intraperitoneal (IP) Oxaliplatin: 200 mg/m2 for 90 minutes, mixed in 250 mL of 5% dextrose solution. For oxaliplatin-based HIPEC, intravenous 5-fluorouracil given at a dose of 400 mg/m2 in 250 mL 0.9% sodium chloride over 10 minutes, co-administered with intravenous leucovorin at 20 mg/m2 in a separate bag of 250 mL 0.9% sodium chloride
DoxorubicinDrug
Part of Arm 3: intraperitoneal (IP) Doxorubicin co-therapy 15 mg/m2 for 60 minutes, given at time = 0 with cisplatin
Hyperthermic Intraperitonial ChemotherapyProcedure or surgery
Hyperthermic Intraperitonial Chemotherapy (HIPEC) with with standardized doses of chemotherapeutic agents as indicated by the subject's Arm assignment
CisplatinDrug
Part of Arms 3 and 4, intraperitoneal (IP)cisplatin co-therapy: 75 mg/m2 for 60 minutes, mixed in 1 L of 0.9% sodium chloride. For cisplatin-based HIPEC, intravenous sodium thiosulfate given as a loading dose of 7.5 g/m2 in 150 mL 0.9% sodium chloride at the time of introducing cisplatin into the perfusion circuit, followed by a 12-hour pump-based infusion of 25.56 g/m2 in 1 L 0.9% sodium chloride
Mitomycin CDrug
Arm 2, intraperitoneal (IP) Mitomycin C monotherapy: dosing divided into two 60-mL syringes, 30 mg per syringe. 30 mg will be given at time = 0, and the remaining 10 mg of the dose will be given at time = 60 minutes. Part of Arm 4: Mitomycin C co-therapy 15 mg/m2 for 60 minutes, given at time = 0 with cisplatin
| Study group | Role | What they receive |
|---|---|---|
| 1/ HIPEC: Oxaliplatin Randomized treatment assignment | Experimental | HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned Receives: Drug: 5-Fluorouracil; Drug: Oxaliplatin; Procedure: Hyperthermic Intraperitonial Chemotherapy |
| 2/ HIPEC: Mitomycin C Randomized treatment assignment | Experimental | HIPEC with intraperitoneal mitomycin C, randomly assigned Receives: Procedure: Hyperthermic Intraperitonial Chemotherapy; Drug: Mitomycin C |
| 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment | Experimental | HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned Receives: Drug: Sodium Thiosulfate; Drug: Doxorubicin; Procedure: Hyperthermic Intraperitonial Chemotherapy; Drug: Cisplatin |
| 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment | Experimental | HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned Receives: Drug: Sodium Thiosulfate; Procedure: Hyperthermic Intraperitonial Chemotherapy; Drug: Cisplatin; Drug: Mitomycin C |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67
percent necrosis and Ki-67 scores will be obtained and used to determine the correlation between each measure by ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and by in vivo intra-operative HIPEC
Measured: approx. 4 days post-HIPEC
Secondary outcomes (4)
To measure Quality of Life by FACT-C and EQ-5D-5L
outcomes from QOL will be reported using descriptive statistics, as well as comparing the results from before to after treatment: physical and mental health-related quality of life, social and emotional wellbeing, and disease-related symptoms
Measured: baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years
To evaluate overall survival for up to 5 years after (last) CRS and HIPEC
median amount of time participant survives from (last) CRS and HIPEC until death or for up to 5 years post-treatment
Measured: death or 5 years post-treatment
To assess germline BAP1 status as a prognostic indicator for progression-free survival (PFS) in participants with peritoneal mesothelioma treated with CRS and HIPEC
Kaplan Meier curves reported separately by BAP1 germline mutation status to describe PFS in participants with peritoneal mesothelioma (only) with and without BAP1 germline mutations
Measured: baseline
To estimate the peritoneal progression-free survival probability
median amount of time participant survives from time of cytoreduction until peritoneal progression, determined for the individual cohorts and treatment arms and compared between arms within cohorts
Measured: baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2021
- Study start19 Oct 2021
- Primary completion30 Dec 2033 (estimated)
- Study completion30 Dec 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peritoneal MesotheliomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrew M Blakely, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04847063
- Sponsor's protocol ID
- 210012
- Other IDs
- 21-C-0012
- Status last verified
- 13 Oct 2026
- First submitted
- 14 Apr 2021
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individualized Response Assessment to Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Peritoneal Mesothelioma or Atypical Mesothelial Proliferation or From Ovarian, Colorectal, or Appendiceal Primaries
- ClinicalTrials.gov ID
- NCT04847063
- Acronym / sponsor ID
- 210012
- Conditions
- Peritoneal Mesothelioma, Peritoneal Carcinomatosis, Ovarian Cancer, Gastrointestinal Cancer, Appendiceal Cancer, Atypical Mesothelial Proliferation
- Keywords
- cytoreduction, organoid model, cell culture model, SMART System, Peritoneal Metastasis, necrosis, Ki-67, cytoreductive surgery (CRS)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 19 Oct 2021 (actual)
- Primary completion
- 30 Dec 2033 (estimated)
- Study completion
- 30 Dec 2034 (estimated)
- First posted
- 15 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is hyperthermic (heated) chemotherapy that washes the inside of the abdomen. CRS with HIPEC may help people with peritoneal carcinomatosis. These are tumors that have spread to the lining of the abdomen from other cancers. Researchers think they can improve the results of CRS with HIPEC treatment on these tumors by choosing the chemotherapy drugs used in HIPEC.
Objective:
To see if HIPEC after CRS can be improved, using either a model called the SMART (Sustained Microenvironment for Analysis of Resected Tissue) System or using 3-D cell culture (organoid) models, in order to test different chemotherapy drugs on tumors that were surgically removed prior to HIPEC treatment (these models are not attached to the body) versus tumors that were treated with HIPEC while still inside the body before being immediately surgically removed.
Eligibility:
Adults ages 18 and older who have peritoneal carcinomatosis that cannot be fully removed safely with surgery.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Electrocardiogram (EKG)
Computed tomography (CT) scan
Other imaging scans, as needed
Tumor biopsy, if needed
Laparoscopy (small cuts are made in the abdomen, and a tube with a light and a camera is used to see the organs in the abdomen), if needed
Participants will enroll in NIH protocol #13C0176. This allows their tumor samples to be used in future research.
Some screening tests may be repeated in the study.
Participants will have CRS. As many of their visible tumors will be removed as possible during surgery except for a few specific tumors left to receive the HIPEC treatment. Then they will receive HIPEC and the remaining tumors will be immediately removed. Participants will be in the hospital for 7-21 days after this surgery (CRS with HIPEC).
Participants will give tumor, fluid samples (from the abdomen during surgery), blood, saliva, cheek swab, and stool for research. They will complete surveys about their health and quality of life.
Participants with peritoneal mesothelioma (mesothelioma primary only) will have genetic (DNA) testing to determine clinical (CLIA level) germline BAP1 status for research use.
Participants will have follow-up visits for up to 5 years from CRS with HIPEC.
If there is disease progression, participants may have CRS with HIPEC again. Participants will then have follow-up visits for up to 5 years from the date of last CRS with HIPEC.
...
Detailed description
Background:
Peritoneal carcinomatosis is uniformly fatal if untreated; improved outcomes are seen with aggressive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).
The selection of chemotherapeutic agent for HIPEC is largely based on primary tumor histology and provider preference as opposed to knowledge of the potential efficacy of a specific agent for an individual patient.
HIPEC is intended to target small or microscopic residual disease following complete cytoreduction; however, the actual efficacy and additional benefit of HIPEC is in question.
Tissue response to simulated ex vivo HIPEC treatment in the SMART System or 3-D cell culture (organoid) models could inform chemotherapeutic agent selection for subsequent cytoreduction and intra-operative in vivo HIPEC treatments.
Objective:
To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67
Eligibility:
Histologically confirmed peritoneal carcinomatosis from peritoneal mesothelioma or atypical mesothelial proliferation, or from appendiceal, colorectal, or ovarian, histologies
Absence of extra-abdominal metastatic disease
Participant deemed able to undergo optimal cytoreduction
Age >= 18 years of age
Design:
This is a Phase I study of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with randomization to one of two accepted HIPEC treatment regimens as determined by primary histology.
At the time of cytoreduction, representative peritoneal tumor biopsies will be obtained before and after intra-operative in vivo HIPEC treatment.
Tumor nodules harvested before intra-operative HIPEC will be placed in either the SMART System or 3-D cell culture (organoid) models, exposed to simulated ex vivo HIPEC treatment, and then perfused or maintained in culture, with subsequent assessment
of percent necrosis and Ki-67.
Tumor nodules harvested immediately after intra-operative HIPEC will be placed in the SMART System or 3-D cell culture (organoid) models and perfused or maintained in culture, with subsequent assessment of percent necrosis and Ki-67.
The correlation of percent necrosis and Ki-67 assessment following simulated ex vivo HIPEC and intra-operative in vivo HIPEC will be determined.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1/ HIPEC: Oxaliplatin Randomized treatment assignment | Experimental | Drug: 5-Fluorouracil, Drug: Oxaliplatin, Procedure: Hyperthermic Intraperitonial ChemotherapyHIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned |
| 2/ HIPEC: Mitomycin C Randomized treatment assignment | Experimental | Procedure: Hyperthermic Intraperitonial Chemotherapy, Drug: Mitomycin CHIPEC with intraperitoneal mitomycin C, randomly assigned |
| 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment | Experimental | Drug: Sodium Thiosulfate, Drug: Doxorubicin, Procedure: Hyperthermic Intraperitonial Chemotherapy, Drug: CisplatinHIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned |
| 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment | Experimental | Drug: Sodium Thiosulfate, Procedure: Hyperthermic Intraperitonial Chemotherapy, Drug: Cisplatin, Drug: Mitomycin CHIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Confirmation of peritoneal carcinomatosis from peritoneal mesothelioma or atypical mesothelial proliferation, or from appendiceal, colorectal, or ovarian, histologies by the Laboratory of Pathology, NCI.
- Measurable or evaluable disease as defined by RECIST v1.1. criteria and/or by peritoneal carcinomatosis index (PCI) score.
- Participants must be assessed to be able to undergo optimal cytoreduction (i.e., completeness of cytoreduction score of 1 or 0) with laparoscopically assessed PCI score threshold as indicated below:
- Age >= 18 years.
- ECOG performance status <= 1 (Karnofsky >= 80%).
Key exclusion criteria (8 listed)
- Participants with known extra-abdominal metastatic disease from the participant s appendiceal, colorectal, ovarian, or peritoneal mesothelioma primary.
- Participants who have received intraperitoneal chemotherapy or other anti-cancer therapy within the last 4 weeks prior to the start of study treatment.
- Participants who have undergone major surgery within the last 12 weeks prior to the start of study treatment.
- History of allergic reactions attributed to platinum-containing compounds.
- History of dihydropyrimidine dehydrogenase deficiency (only participants with appendiceal or colorectal cancer).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium ThiosulfatePart of Arms 3 and 4, for cisplatin-based HIPEC: intravenous sodium thiosulfate given as a loading dose of 7.5 g/m2 in 150 mL 0.9% sodium chloride at the time of introducing cisplatin into the perfusion circuit, followed by a 12-hour pump-based infusion of 25.56 g/m2 in 1 L 0.9% sodium chloride | Drug | 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment, 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment |
| 5-FluorouracilPart of Arm 1, for oxaliplatin-based HIPEC: intravenous 5-fluorouracil given at a dose of 400 mg/m2 in 250 mL 0.9% sodium chloride over 10 minutes, co-administered with intravenous leucovorin at 20 mg/m2 in a separate bag of 250 mL 0.9% sodium chloride | Drug | 1/ HIPEC: Oxaliplatin Randomized treatment assignment |
| OxaliplatinArm 1, intraperitoneal (IP) Oxaliplatin: 200 mg/m2 for 90 minutes, mixed in 250 mL of 5% dextrose solution. For oxaliplatin-based HIPEC, intravenous 5-fluorouracil given at a dose of 400 mg/m2 in 250 mL 0.9% sodium chloride over 10 minutes, co-administered with intravenous leucovorin at 20 mg/m2 in a separate bag of 250 mL 0.9% sodium chloride | Drug | 1/ HIPEC: Oxaliplatin Randomized treatment assignment |
| DoxorubicinPart of Arm 3: intraperitoneal (IP) Doxorubicin co-therapy 15 mg/m2 for 60 minutes, given at time = 0 with cisplatin | Drug | 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment |
| Hyperthermic Intraperitonial ChemotherapyHyperthermic Intraperitonial Chemotherapy (HIPEC) with with standardized doses of chemotherapeutic agents as indicated by the subject's Arm assignment | Procedure or surgery | 1/ HIPEC: Oxaliplatin Randomized treatment assignment, 2/ HIPEC: Mitomycin C Randomized treatment assignment, 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment, 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment |
| CisplatinPart of Arms 3 and 4, intraperitoneal (IP)cisplatin co-therapy: 75 mg/m2 for 60 minutes, mixed in 1 L of 0.9% sodium chloride. For cisplatin-based HIPEC, intravenous sodium thiosulfate given as a loading dose of 7.5 g/m2 in 150 mL 0.9% sodium chloride at the time of introducing cisplatin into the perfusion circuit, followed by a 12-hour pump-based infusion of 25.56 g/m2 in 1 L 0.9% sodium chloride | Drug | 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment, 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment |
| Mitomycin CArm 2, intraperitoneal (IP) Mitomycin C monotherapy: dosing divided into two 60-mL syringes, 30 mg per syringe. 30 mg will be given at time = 0, and the remaining 10 mg of the dose will be given at time = 60 minutes. Part of Arm 4: Mitomycin C co-therapy 15 mg/m2 for 60 minutes, given at time = 0 with cisplatin | Drug | 2/ HIPEC: Mitomycin C Randomized treatment assignment, 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment |
Primary outcome
To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67
Time frame: approx. 4 days post-HIPEC
percent necrosis and Ki-67 scores will be obtained and used to determine the correlation between each measure by ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and by in vivo intra-operative HIPEC
4 secondary outcomes
To measure Quality of Life by FACT-C and EQ-5D-5L
Time frame: baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years
To evaluate overall survival for up to 5 years after (last) CRS and HIPEC
Time frame: death or 5 years post-treatment
To assess germline BAP1 status as a prognostic indicator for progression-free survival (PFS) in participants with peritoneal mesothelioma treated with CRS and HIPEC
Time frame: baseline
To estimate the peritoneal progression-free survival probability
Time frame: baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request.
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A Beta-only IL-2 ImmunoTherapY Study
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Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma
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First-line Treatment With Dual Immunotherapy Combined With Anti-angiogenesis for Unresectable Advanced Malignant Peritoneal Mesothelioma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrew M Blakely, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sodium Thiosulfate, 5-Fluorouracil and Oxaliplatin in people with Peritoneal Mesothelioma and Peritoneal Carcinomatosis, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stephanie N Canady, R.N. ((240) 858-7573, stephanie.canady@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the correlation between ex vivo simulated HIPEC in the SMART System or 3-D cell culture (organoid) models, and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67 (time frame: approx. 4 days post-HIPEC). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.