Individualized Response Assessment to Heated Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Ovarian, Colorectal, Appendiceal, or Peritoneal Mesothelioma Histologies

NCT ID: NCT04847063

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-19
• Study Completion Date: 2031-12-30

Brief Summary

Background:

Cytoreductive surgery (CRS) removes tumors in the abdomen. HIPEC is heated chemotherapy that washes the abdomen. CRS and 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 results of CRS and HIPEC by choosing the chemotherapy drugs used in HIPEC.

Objective:

To see if HIPEC after CRS can be improved, by testing different chemotherapy drugs, using a model called the SMART (Sample Microenvironment of Resected Metastatic Tumor) System.

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

Computed tomography (CAT) scan

Other imaging scans, as needed

Electrocardiogram (EKG)

Tumor biopsy, if needed

Laparoscopy. Small cuts will be made in the abdomen. A tube with a light and a camera will be used to see their organs.

Some screening tests will be repeated in the study.

Participants will enroll in NIH protocol #13C0176. This allows their tumor samples to be used in future research.

Participants will have CRS. As many of their visible tumors will be removed as possible. They will also have HIPEC. Two thin tubes will be put in their abdomen. They will get chemotherapy through one tube. It will be drained out through the other tube. They will be in the hospital for 7-21 days after surgery.

Participants will give tumor, blood, and fluid samples for research. They will complete surveys about their health and quality of life.

Participants will have follow-up visits over 5 years.

Detailed Description

Background:

Peritoneal carcinomatosis is uniformly fatal if untreated; improved outcomes are seen with aggressive cytoreductive surgery (CRS) and heated 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.

The SMART System provides an ideal platform upon which to perfuse small peritoneal tumor tissue implants and simulate HIPEC treatment ex vivo.

Tissue response to simulated ex vivo HIPEC treatment in the SMART System 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 and in vivo HIPEC with respect to two measures of response to treatment: percent necrosis and Ki-67

Eligibility:

Histologically confirmed peritoneal carcinomatosis from appendiceal, colorectal, ovarian, or peritoneal mesothelioma histologies

Absence of extra-abdominal metastatic disease

Participant deemed able to undergo complete cytoreduction

Age >= 18 years of age

Design:

This is a Phase I study of cytoreductive surgery (CRS) and heated 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 the SMART System, exposed to simulated ex vivo HIPEC treatment, and then perfused, with subsequent assessment of percent necrosis and Ki-67.

Tumor nodules harvested immediately after intra-operative HIPEC will be placed in the SMART System and perfused, 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 Carcinomatosis; Peritoneal Mesothelioma; Ovarian Cancer; Gastrointestinal Cancer; Appendiceal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

1/ HIPEC: Oxaliplatin Randomized treatment assignment

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

Group Type: EXPERIMENTAL

Heated Intraperitonial Chemotherapy

Intervention Type: PROCEDURE

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

Oxaliplatin

Intervention Type: 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

5-Fluorouracil

Intervention Type: 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

2/ HIPEC: Mitomycin C Randomized treatment assignment

HIPEC with intraperitoneal mitomycin C, randomly assigned

Group Type: EXPERIMENTAL

Mitomycin C

Intervention Type: 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

Heated Intraperitonial Chemotherapy

Intervention Type: PROCEDURE

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

3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignme

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

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: 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

Heated Intraperitonial Chemotherapy

Intervention Type: PROCEDURE

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

Doxorubicin

Intervention Type: DRUG

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

Sodium Thiosulfate

Intervention Type: 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

4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignme

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

Group Type: EXPERIMENTAL

Mitomycin C

Intervention Type: 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

Cisplatin

Intervention Type: 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

Heated Intraperitonial Chemotherapy

Intervention Type: PROCEDURE

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

Sodium Thiosulfate

Intervention Type: 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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Heated Intraperitonial Chemotherapy

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

Intervention Type: PROCEDURE

Doxorubicin

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Confirmation of peritoneal carcinomatosis from appendiceal, colorectal, ovarian, or peritoneal mesothelioma 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 complete cytoreduction, with laparoscopically assessed PCI score thresholds as indicated below:

• Primary Histology: Appendiceal/Colorectal/Ovarian / PCI Cutoff for Eligibility: Total Score < 20 (out of 39 possible points)
• Primary Histology: Mesothelioma / 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 normal institutional limits
• 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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew M Blakely, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Stephanie N Canady, R.N.

Role: CONTACT

stephanie.canady@nih.gov

(240) 858-7573

Andrew M Blakely, M.D.

Role: CONTACT

andrew.blakely@nih.gov

(240) 760-7647

Facility Contacts

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

Role: primary

888-624-1937

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2021-C-0012.html

NIH Clinical Center Detailed Web Page

Other Identifiers

21-C-0012

Identifier Type: -

Identifier Source: secondary_id

210012

Identifier Type: -

Identifier Source: org_study_id