Recruiting
Phase 1

HIPEC

Sponsor:

National Cancer Institute (NCI)

Code:

NCT04847063

Conditions

Peritoneal Mesothelioma

Peritoneal Carcinomatosis

Ovarian Cancer

Gastrointestinal Cancer

Appendiceal Cancer

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Sodium Thiosulfate

5-Fluorouracil

Oxaliplatin

Doxorubicin

Hyperthermic Intraperitonial Chemotherapy

Study Details

Brief 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.

Conditions

Peritoneal Mesothelioma

Peritoneal Carcinomatosis

Ovarian Cancer

Gastrointestinal Cancer

Appendiceal Cancer

Study ID

NCT04847063

Start date

Oct 19, 2021

Status verified date

Oct 13, 2026

Completion date

Dec 30, 2034

Anticipated

Primary completion date

Dec 30, 2033

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:
  • 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.
  • 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 .

EXCLUSION CRITERIA:

  • 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.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

experimental: 1/ HIPEC: Oxaliplatin Randomized treatment assignment

HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned

experimental: 2/ HIPEC: Mitomycin C Randomized treatment assignment

HIPEC with intraperitoneal mitomycin C, randomly assigned

experimental: 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment

HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned

experimental: 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment

HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned

Interventions

Sodium Thiosulfate

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-Fluorouracil

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

Oxaliplatin

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

Doxorubicin

Part of Arm 3: intraperitoneal (IP) Doxorubicin co-therapy 15 mg/m2 for 60 minutes, given at time = 0 with cisplatin

Hyperthermic Intraperitonial Chemotherapy

Hyperthermic Intraperitonial Chemotherapy (HIPEC) with with standardized doses of chemotherapeutic agents as indicated by the subject's Arm assignment

Cisplatin

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 C

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

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 ]

Central Contacts and Locations

Central contacts

Stephanie N Canady, R.N.

(240) 858-7573stephanie.canady@nih.gov

Andrew M Blakely, M.D.

(240) 760-7647andrew.blakely@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

888-624-1937

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Oct 16, 2026

Last verified

Oct 13, 2026

Keywords

  • cytoreduction
  • organoid model
  • cell culture model
  • SMART System
  • Peritoneal Metastasis
  • necrosis
  • Ki-67
  • cytoreductive surgery (CRS)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-10-16. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.