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

NCT04847063 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21001221-C-0012
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Ovarian Cancer; Gastrointestinal Cancer; Appendiceal Cancer; Peritoneal Carcinomatosis; Peritoneal Mesothelioma; Atypical Mesothelial Proliferation; Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  approx. 4 days post-HIPEC

Secondary Outcomes (4)

• To measure Quality of Life by FACT-C and EQ-5D-5L

  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

  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

  baseline

• To estimate the peritoneal progression-free survival probability

  baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years

Study Arms (4)

1/ HIPEC: Oxaliplatin Randomized treatment assignment

EXPERIMENTAL

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

Drug: 5-Fluorouracil; Drug: Oxaliplatin; Procedure: Hyperthermic Intraperitonial Chemotherapy

2/ HIPEC: Mitomycin C Randomized treatment assignment

EXPERIMENTAL

HIPEC with intraperitoneal mitomycin C, randomly assigned

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

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

Drug: Sodium Thiosulfate; Procedure: Hyperthermic Intraperitonial Chemotherapy; Drug: Cisplatin; Drug: Mitomycin C

Interventions

Mitomycin C DRUG

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

2/ HIPEC: Mitomycin C Randomized treatment assignment; 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment

Cisplatin DRUG

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

3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment; 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment

Doxorubicin DRUG

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

3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment

Oxaliplatin DRUG

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

1/ HIPEC: Oxaliplatin Randomized treatment assignment

5-Fluorouracil DRUG

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

1/ HIPEC: Oxaliplatin Randomized treatment assignment

Sodium Thiosulfate DRUG

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

3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignment; 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignment

Hyperthermic Intraperitonial Chemotherapy PROCEDURE

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

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

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Peritoneal Neoplasms; Ovarian Neoplasms; Gastrointestinal Neoplasms; Appendiceal Neoplasms; Colorectal Neoplasms; Necrosis

Interventions

sodium thiosulfate; Fluorouracil; Oxaliplatin; Doxorubicin; Cisplatin; Mitomycin

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Gastrointestinal Diseases; Cecal Neoplasms; Intestinal Neoplasms; Cecal Diseases; Intestinal Diseases; Colonic Diseases; Rectal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Mitomycins; Indolequinones; Quinones; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Andrew M Blakely, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie N Canady, R.N.

CONTACT

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

Andrew M Blakely, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: April 15, 2021
• Study Start: October 19, 2021
• Primary Completion (Estimated): December 30, 2033
• Study Completion (Estimated): December 30, 2034
• Last Updated: April 14, 2026

Record last verified: 2026-03-26

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)