Phase I Trial HIPEC With Nal-irinotecan

NCT04088786 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2019-00059 HIPEC Nal-IRI
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Peritoneal Cancer; Pseudomyxoma Peritonei; Mucinous Adenocarcinoma; Mucinous Tumor; Colorectal Cancer; Gastric Cancer; Primary Peritoneal Carcinoma; Mesothelioma

Keywords

HIPEC; nal-irinotecan

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  To assess the safety and feasibility of administering nanoliposmal irinotecan intraperitoneally following cytoreductive surgery.

  Up to 4 weeks post surgery

Secondary Outcomes (2)

• Plasmatic dosages

  48 hours

• Disease Free survival

  6 months

Study Arms (1)

Active

EXPERIMENTAL

Cytoreductive surgery (CRS) followed by study treatment with nanoliposomal irinotecan administered intraperitoneally.

Drug: nanoliposomal irinotecan

Interventions

nanoliposomal irinotecan DRUG

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.

Active

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥18 years
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Patients must be candidates for grossly complete cytoreduction surgery with life expectancy greater than 3 months
• 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
• 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.
• 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.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients with peritoneal disease considered to be unresectable according to preoperative clinical criteria.
• 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.
• Large burden visceral metastases or extra-abdominal metastases.
• 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.
• Patients may not be receiving any other investigational agents.
• History of allergic reactions to nal-IRI or irinotecan.
• 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.
• Pregnant or breast-feeding women are excluded from this study.
• 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.

Sponsors & Collaborators

• Stony Brook University: lead
• Ipsen: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator
• University of Iowa: collaborator

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794, United States

Location

Related Publications (1)

• McDonald HG, Cassim EB, Harper MM, Burke EE, Marcinkowski EF, Cavnar MJ, Pandalai PK, Kim J. The Development of Investigator-Initiated Clinical Trials in Surgical Oncology. Surg Oncol Clin N Am. 2023 Jan;32(1):13-25. doi: 10.1016/j.soc.2022.07.003. Epub 2022 Nov 3.

  PMID: 36410913 DERIVED

MeSH Terms

Conditions

Pseudomyxoma Peritonei; Adenocarcinoma, Mucinous; Neoplasms, Cystic, Mucinous, and Serous; Colorectal Neoplasms; Stomach Neoplasms; Mesothelioma

Interventions

irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Adenoma; Neoplasms, Mesothelial

Study Officials

• Minsig Choi, MD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

• Joseph Kim, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

• Georgios Georgakis, MD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: All eligible patients will be treated with the study drug.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor of Medicine

Model Details: This is a 3+3 dose-finding cohort design.

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 13, 2019
• Study Start: October 22, 2019
• Primary Completion: October 11, 2021
• Study Completion: April 14, 2022
• Last Updated: May 6, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)