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Phase I Trial HIPEC With Nal-irinotecan

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04088786
Recruitment Status : Completed
First Posted : September 13, 2019
Last Update Posted : May 6, 2022
Barbara Ann Karmanos Cancer Institute
University of Iowa
Information provided by (Responsible Party):
minsig Choi, Stony Brook University

Brief Summary:
The purpose of this study is to assess the effectiveness and safety of intraperitoneal administration of heated nanoliposomal Irinotecan in cytoreductive surgery (CRS), which is surgery designed to remove as much of the cancer as possible, and heated intraperitoneal chemotherapy (HIPEC) procedures.

Condition or disease Intervention/treatment Phase
Peritoneal Cancer Pseudomyxoma Peritonei Mucinous Adenocarcinoma Mucinous Tumor Colorectal Cancer Gastric Cancer Primary Peritoneal Carcinoma Mesothelioma Drug: nanoliposomal irinotecan Phase 1

Detailed Description:
Cytoreductive surgery and heated intraperitoneal chemotherapy consists of two parts: the first is the surgical removal of all grossly visible deposits of cancer from the abdomen; and the second is application of heated chemotherapy in salt water at the same time as the removal of the visible cancer. HIPEC is an alternative method of delivering chemotherapy. Traditional chemotherapy is injected into a vein, while HIPEC applies chemotherapy drugs warmed up by an FDA-approved machine to 108 degrees Fahrenheit directly into the abdomen during surgery, making it an option for cancers that originated in or have spread to the abdominal cavity. Standard treatment in this manner usually includes Mitomycin C or Cisplatin as its chemotherapy agents. In this study, the investigators will use nanoliposomal irinotecan as the chemotherapy agent. Irinotecan is FDA approved for the treatment of pancreatic cancer.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a 3+3 dose-finding cohort design.
Masking: None (Open Label)
Masking Description: All eligible patients will be treated with the study drug.
Primary Purpose: Treatment
Official Title: Phase I Trial of Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy With Nanoliposomal Irinotecan in Patients With Peritoneal Surface Malignancies
Actual Study Start Date : October 22, 2019
Actual Primary Completion Date : October 11, 2021
Actual Study Completion Date : April 14, 2022

Arm Intervention/treatment
Experimental: Active
Cytoreductive surgery (CRS) followed by study treatment with nanoliposomal irinotecan administered intraperitoneally.
Drug: nanoliposomal irinotecan
The starting dose of nal-IRI will be 70 mg/m2 (cohort level 1) applied for 30 min using a closed HIPEC technique following completion of cytoreductive surgery. If there is dose limiting toxicity (DLT) in cohort level 1, then the dose will be reduced the dosage of the next cohort to 50 mg/m2 (cohort level 0). If there is no DLT, the dose of nal-IRI will be increased to 140 mg/m2, 210 mg/m2 and 280 mg/m2 . If one of the patients experiences DLT, then the cohort will expand to 6 patients and accrual to the current dose level and dose escalation will stop if 2 or more patients experience a DLT at a given dose level.

Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Up to 4 weeks post surgery ]
    To assess the safety and feasibility of administering nanoliposmal irinotecan intraperitoneally following cytoreductive surgery.

Secondary Outcome Measures :
  1. Plasmatic dosages [ Time Frame: 48 hours ]
    Determine the correlation of intraperitoneal dosages of nanoliposomal irinotecan with plasma blood levels using pharmacokinetic analysis

  2. Disease Free survival [ Time Frame: 6 months ]
    Assess the efficacy of intraperitoneal administration of nanoliposomal irinotecan relating to disease free survival.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with pseudomyxoma peritonei or peritoneal carcinomatosis of digestive origin or primary peritoneum: appendiceal mucinous tumor or adenocarcinoma (including goblet cell cancer and signet ring cell cancer), colorectal cancer, gastric cancer, primary peritoneal adenocarcinoma, and mesothelioma; regardless of the number of prior treatment lines. Diagnosis of peritoneal metastasis to be confirmed via either clinical or histopathology assessment.
  2. Age ≥18 years
  3. Eastern Cooperative Oncology Group performance status of 0 or 1
  4. Patients must be candidates for grossly complete cytoreduction surgery with life expectancy greater than 3 months
  5. Patients must have normal organ and marrow function as defined below:

    • absolute neutrophil count >1,500/microliter (mcL) and white blood cells > 4000/mm3
    • platelets >75,000/microliters
    • total bilirubin < 3x upper limit normal for institutional limits
    • aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) <2.5x institutional upper limit of normal
    • creatinine within normal institutional limits
  6. Documentation of resectable disease extent by radiographic peritoneal carcinomatosis index (PCI) score or preoperative diagnostic surgery/laparoscopy with preoperative measurements taken within 6 weeks of study entry.
  7. Women of child-bearing potential and men must agree to use adequate contraception (barrier or hormonal plus barrier method of birth control; abstinence) prior to study entry and for the duration of study participation (at least first 6 months). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients with peritoneal disease considered to be unresectable according to preoperative clinical criteria.
  2. Patients who undergo debulking for palliation with persistence of gross residual disease (complete of cytoreduction score 3, CC=3) will be ineligible for the study.
  3. Large burden visceral metastases or extra-abdominal metastases.
  4. Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. There is no limit on the number of prior lines of chemotherapy.
  5. Patients may not be receiving any other investigational agents.
  6. History of allergic reactions to nal-IRI or irinotecan.

7 Uncontrolled ongoing 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.

8 Pregnant or breast-feeding women are excluded from this study.

9 HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

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 identifier (NCT number): NCT04088786

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United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, New York
Stony Brook University Cancer Center
Stony Brook, New York, United States, 11794
Sponsors and Collaborators
Stony Brook University
Barbara Ann Karmanos Cancer Institute
University of Iowa
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Principal Investigator: Minsig Choi, MD Stony Brook University
Principal Investigator: Joseph Kim, MD University of Kentucky
Principal Investigator: Georgios Georgakis, MD Stony Brook University
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Responsible Party: minsig Choi, Clinical Associate Professor of Medicine, Stony Brook University Identifier: NCT04088786    
Other Study ID Numbers: 2019-00059 HIPEC Nal-IRI
First Posted: September 13, 2019    Key Record Dates
Last Update Posted: May 6, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by minsig Choi, Stony Brook University:
Additional relevant MeSH terms:
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Adenocarcinoma, Mucinous
Pseudomyxoma Peritonei
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Neoplasms, Cystic, Mucinous, and Serous
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents