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

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT04847063
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 120 Years
Healthy Volunteers
Not accepted

Interventions

  • 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
  • 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
  • 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
  • Doxorubicin — DRUG
    Part of Arm 3: intraperitoneal (IP) Doxorubicin co-therapy 15 mg/m2 for 60 minutes, given at time = 0 with cisplatin
  • Hyperthermic Intraperitonial Chemotherapy — PROCEDURE
    Hyperthermic Intraperitonial Chemotherapy (HIPEC) with with standardized doses of chemotherapeutic agents as indicated by the subject's Arm 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
  • 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

Study Details

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.

Key Dates

Start date
Oct 19, 2021
Status verified
Mar 2026
Primary completion
Dec 30, 2033
Completion
Dec 30, 2034

Study Design

Enrollment
60 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC

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

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

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
888-624-1937

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