Individualized Response Assessment to Heated Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Ovarian, Colorectal, Appendiceal, or Peritoneal Mesothelioma Histologies
- Conditions
- Peritoneal MesotheliomaOvarian CancerGastrointestinal CancerAppendiceal CancerPeritoneal Carcinomatosis
- Interventions
- Procedure: Heated Intraperitonial Chemotherapy
- Registration Number
- NCT04847063
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1/ HIPEC: Oxaliplatin Randomized treatment assignment Heated Intraperitonial Chemotherapy HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned 1/ HIPEC: Oxaliplatin Randomized treatment assignment 5-Fluorouracil HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignme Heated Intraperitonial Chemotherapy HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned 1/ HIPEC: Oxaliplatin Randomized treatment assignment Oxaliplatin HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned 2/ HIPEC: Mitomycin C Randomized treatment assignment Heated Intraperitonial Chemotherapy HIPEC with intraperitoneal mitomycin C, randomly assigned 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignme Mitomycin C HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignme Heated Intraperitonial Chemotherapy HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned 2/ HIPEC: Mitomycin C Randomized treatment assignment Mitomycin C HIPEC with intraperitoneal mitomycin C, randomly assigned 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignme Sodium Thiosulfate HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignme Sodium Thiosulfate HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignme Doxorubicin HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignme Cisplatin HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignme Cisplatin HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned
- Primary Outcome Measures
Name Time Method 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 approx. 4 days post-HIPEC 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 and by in vivo intra-operative HIPEC
- Secondary Outcome Measures
Name Time Method 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, separately within each cohort and arm subset, as well as within... approx. 4 days post-HIPEC Tumor tissue responses to ex vivo simulated HIPEC and in vivo HIPEC regimens will be assessed by an intramural pathologist using percent tissue necrosis and Ki-67 scoring, both to the nearest 10 percent. These assessments will be incorporated into pathology reports following cytoreductive surgery with HIPEC
To estimate the peritoneal progression-free survival probability, separately by arms and by cohorts, in a preliminary fashion baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years median amount of time participant survives from time of cytoreduction until peritoneal progression, assessed for the individual cohorts and treatment arms and also compared between arms within cohorts
To estimate the peritoneal progression-free survival probability as a function of tissue response to ex vivo simulated HIPEC in the SMART System and in vivo HIPEC, as assessed by percent necrosis and Ki-67, in a preliminary fashion baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years median amount of time participant survives from time of cytoreduction until peritoneal progression, as assessed in tissue response by percent necrosis and Ki-67
To evaluate overall survival for up to 5 years after CRS and HIPEC death or 5 years post-treatment median amount of time participant survives from CRS and HIPEC until death or for up to 5 years post-treatment
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 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
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States