Health TrialsbyHealthPanel

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

ConditionsPeritoneal MesotheliomaPeritoneal CarcinomatosisOvarian CancerGastrointestinal CancerAppendiceal CancerAtypical Mesothelial ProliferationColorectal Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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.

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)

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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/Surgery

    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

Treatment groups

60 Participants
are divided into 4 treatment groups
Group A: 1/ HIPEC: Oxaliplatin Randomized treatment assignmentExperimental treatment 3 interventions
Group B: 2/ HIPEC: Mitomycin C Randomized treatment assignmentExperimental treatment 2 interventions
Group C: 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignmentExperimental treatment 4 interventions
Group D: 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignmentExperimental treatment 4 interventions

Trial outcomes

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

Time frame
approx. 4 days post-HIPEC

Secondary outcomes

1

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

outcomes from QOL will be reported using descriptive statistics, as well as comparing the results from before to after treatment: physical and mental health-related quality of life, social and emotional wellbeing, and disease-related symptoms

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

To evaluate overall survival for up to 5 years after (last) CRS and HIPEC

median amount of time participant survives from (last) CRS and HIPEC until death or for up to 5 years post-treatment

Time frame
death or 5 years post-treatment
3

To assess germline BAP1 status as a prognostic indicator for progression-free survival (PFS) in participants with peritoneal mesothelioma treated with CRS and HIPEC

Kaplan Meier curves reported separately by BAP1 germline mutation status to describe PFS in participants with peritoneal mesothelioma (only) with and without BAP1 germline mutations

Time frame
baseline
4

To estimate the peritoneal progression-free survival probability

median amount of time participant survives from time of cytoreduction until peritoneal progression, determined for the individual cohorts and treatment arms and compared between arms within cohorts

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
Apply now