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

Last updated: April 11, 2026
Sponsor: National Cancer Institute (NCI)
Overall Status: Active - Recruiting

Phase

1

Condition

Abdominal Cancer

Gastric Cancer

Peritoneal Cancer

Treatment

Sodium Thiosulfate

5-Fluorouracil

Mitomycin C

Clinical Study ID

NCT04847063
210012
21-C-0012
  • Ages 18-120
  • All Genders

Study 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. 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.

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:

  • Confirmation of peritoneal carcinomatosis from peritoneal mesothelioma or atypicalmesothelial proliferation, or from appendiceal, colorectal, or ovarian, histologiesby the Laboratory of Pathology, NCI.

  • Measurable or evaluable disease as defined by RECIST v1.1. criteria and/or byperitoneal 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 PCIscore 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 / PCICutoff for Eligibility: Total Score <= 30 (out of 39 possible points)

  • Age >= 18 years.

  • 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 tofather a child must agree to use adequate contraception (hormonal or barrier methodof birth control; abstinence) prior to study entry and for 180 days after last studytreatment.

  • Ability of participant to understand and the willingness to sign a written informedconsent document.

  • Ability and willingness of the participant to co-enroll on the tissue collectionprotocol 13C0176, Tumor, Normal Tissue and Specimens from Patients UndergoingEvaluation or Surgical Resection of Solid Tumors .

Exclusion

EXCLUSION CRITERIA:

  • Participants with known extra-abdominal metastatic disease from the participant sappendiceal, colorectal, ovarian, or peritoneal mesothelioma primary.

  • Participants who have received intraperitoneal chemotherapy or other anti-cancertherapy 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 thestart of study treatment.

  • History of allergic reactions attributed to platinum-containing compounds.

  • History of dihydropyrimidine dehydrogenase deficiency (only participants withappendiceal or colorectal cancer).

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

  • Pregnant individuals are excluded from this study because the protocol involvesmajor abdominal surgery and chemotherapeutic agents with the potential forteratogenic or abortifacient effects. Note: Due to an unknown but potential risk foradverse events in nursing infants secondary to treatment of the participant, nursing (including breastfeeding) should be discontinued if the participant is undergoingtreatment (i.e., nursing participants must agree to discontinue nursing activities).

  • HIV-positive participants with detectable viral load despite antiretroviral therapyare ineligible because of participants increased risk of lethal infections whentreated with marrow-suppressive therapy. HIV-positive participants who haveundetectable viral load on antiretroviral therapy may be considered for this studyonly after consultation with a NIAID physician.

Study Design

Total Participants: 60
Treatment Group(s): 8
Primary Treatment: Sodium Thiosulfate
Phase: 1
Study Start date:
October 19, 2021
Estimated Completion Date:
December 30, 2034

Study 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.

Connect with a study center

  • National Institutes of Health Clinical Center

    Bethesda, Maryland 20892
    United States

    Active - Recruiting

  • National Institutes of Health Clinical Center

    Bethesda 4348599, Maryland 4361885 20892
    United States

    Site Not Available

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