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

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ClinicalTrials.gov Identifier: NCT04847063
Recruitment Status : Recruiting
First Posted : April 15, 2021
Last Update Posted : September 6, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( 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.


Condition or disease Intervention/treatment Phase
Peritoneal Carcinomatosis Peritoneal Mesothelioma Ovarian Cancer Gastrointestinal Cancer Appendiceal Cancer Drug: Mitomycin C Drug: Cisplatin Procedure: Heated Intraperitonial Chemotherapy Drug: Doxorubicin Drug: Oxaliplatin Drug: 5-Fluorouracil Drug: Sodium Thiosulfate Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Individualized Response Assessment to Heated Intraperitoneal Chemotherapy (HIPEC) for the Treatment of Peritoneal Carcinomatosis From Ovarian, Colorectal, Appendiceal, or Peritoneal Mesothelioma Histologies
Actual Study Start Date : October 19, 2021
Estimated Primary Completion Date : December 30, 2030
Estimated Study Completion Date : December 30, 2031


Arm Intervention/treatment
Experimental: 1/ HIPEC: Oxaliplatin Randomized treatment assignment
HIPEC with intraperitoneal oxaliplatin and IV 5-FU, randomly assigned
Procedure: Heated Intraperitonial Chemotherapy
Heated Intraperitonial Chemotherapy (HIPEC) with with standardized doses of chemotherapeutic agents as indicated by the subject's Arm assignment

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

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

Experimental: 2/ HIPEC: Mitomycin C Randomized treatment assignment
HIPEC with intraperitoneal mitomycin C, randomly assigned
Drug: 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

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

Experimental: 3/ HIPEC: Cisplatin, Doxorubicin Randomized treatment assignme
HIPEC with intraperitoneal cisplatin and doxorubicin, in addition to IV sodium thiosulfate, randomly assigned
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

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

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

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

Experimental: 4/ HIPEC: Cisplatin, Mitomycin C Randomized treatment assignme
HIPEC with intraperitoneal cisplatin and mitomycin C, in addition to IV sodium thiosulfate, randomly assigned
Drug: 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

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

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

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




Primary Outcome Measures :
  1. 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 [ Time Frame: 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 :
  1. 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... [ Time Frame: 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

  2. To estimate the peritoneal progression-free survival probability, separately by arms and by cohorts, in a preliminary fashion [ Time Frame: baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years ]
    median amount of time subject survives from time of cytoreduction until peritoneal progression, assessed for the individual cohorts and treatment arms and also compared between arms within cohorts

  3. 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 [ Time Frame: baseline, every 3 months post-treatment for 2 years, than every 6 months for a total of 5 years ]
    median amount of time subject survives from time of cytoreduction until peritoneal progression, as assessed in tissue response by percent necrosis and Ki-67

  4. To evaluate overall survival for up to 5 years after CRS and HIPEC [ Time Frame: death or 5 years post-treatment ]
    median amount of time subject survives from CRS and HIPEC until death or for up to 5 years post-treatment

  5. To measure Quality of Life by FACT-C and EQ-5D-5L [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 PCI score <= 30 at the time of laparoscopy.
  • Age >= 18 years.
  • ECOG performance status <= 1 (Karnofsky >= 80%).
  • Participants must have adequate organ and marrow function as defined below:

    • Leukocytes >= 3,000/mcL
    • 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)
    • 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, women of childbearing potential and men 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; should a woman suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • 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 deificiency (appendiceal or colorectal

cancer patients only).

  • 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 women are excluded from this study because the protocol involves major abdominal surgery and chemotherapeutic agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is undergoing treatment.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04847063


Contacts
Layout table for location contacts
Contact: Audra A Satterwhite, R.N. (240) 858-3552 audra.satterwhite@nih.gov
Contact: Andrew M Blakely, M.D. (240) 760-7647 andrew.blakely@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Andrew M Blakely, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04847063    
Other Study ID Numbers: 210012
21-C-0012
First Posted: April 15, 2021    Key Record Dates
Last Update Posted: September 6, 2022
Last Verified: July 27, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
cytoreductive surgery (CRS)
SMART System
necrosis
Ki-67
Peritoneal Metastasis
Additional relevant MeSH terms:
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Mesothelioma
Mesothelioma, Malignant
Gastrointestinal Neoplasms
Carcinoma
Peritoneal Neoplasms
Appendiceal Neoplasms
Neoplasms by Site
Neoplasms
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Abdominal Neoplasms
Peritoneal Diseases
Cecal Neoplasms
Intestinal Neoplasms
Cecal Diseases
Intestinal Diseases
Sodium thiosulfate
Cisplatin
Doxorubicin