Phase II Study of the Effects of Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Gastric Cancer

A Phase IIa Study of Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and PD-L1 Expression in Gastric Cancer With Peritoneal Metastases

To assess if PD-L1 expression can be upregulated in peritoneal metastases from gastric cancer after the administration of HIPEC with greater frequency compared to systemic chemotherapy alone

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Peritoneal Carcinomatosis
• Intervention / Treatment: Drug: Cisplatin; Drug: Mitomycin

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cancer Clinical Trials Office; Phone Number: 1-855-702-8222; Email: cancerclinicaltrials@bsd.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University Of Chicago
      • Principal Investigator: Ardaman Shergill, MD
      • Contact: Cancer Clinical Trials Office; Phone Number: 855-702-8222; Email: cancerclinicaltrials@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histologically confirmed GC/PM only and/or positive peritoneal cytology, who have completed prior systemic chemotherapy for a minimum of 2 to 4 months duration.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of HIPEC for GC/PM in patients under 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).

• Patients must have adequate organ and marrow function as defined below:

  • leukocytes ≥3,000/mcL
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • total bilirubin ≤ institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
  • creatinine ≤ institutional ULN OR
  • glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2 (see Appendix B).
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Expected survival greater than 3 months.
• Because cisplatin and Mitomycin C are pregnancy category D and potentially teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of the study.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients with coexistence of another untreated malignant neoplasm other than basal cell carcinoma of the skin within the last five years.
• Sites of metastases other than loco-regional lymph nodes and peritoneum (ex. Visceral metastases such as liver, lungs, bone, brain).
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin and Mitomycin C.
• Patients with uncontrolled intercurrent illness.
• Patients with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because cisplatin and Mitomycin C are class D 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 with cisplatin and Mitomycin C, breastfeeding should be discontinued if the mother is treated with cisplatin and Mitomycin C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Drug Administration Period

Drug: Cisplatin; Laparoscopic HIPEC will be performed at a maximum of two (2) times spaced approximately 6 weeks apart. The dosing of the drugs will be the same during each administration but adjusted if needed based on lab work. The typical dosages are 200mg of Cisplatin; Drug: Mitomycin; Laparoscopic HIPEC will be performed at a maximum of two (2) times spaced approximately 6 weeks apart. The dosing of the drugs will be the same during each administration but adjusted if needed based on lab work. The typical dosages are 30mg of Mitomycin C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The PD-L1 expression can be upregulated after administration of HIPEC with greater frequency	To examine if PD-L1 expression can be upregulated in peritoneal metastases from gastric cancer after the administration of HIPEC with greater frequency compared to systemic chemotherapy alone. PD-L1 expression will be measured quantitatively by combined positive score (CPS), with upregulation defined as an quantitative increase in PD-L1 expression via CPS compared to the previously measured timepoint (baseline CPS of 0).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of conversion to resectability with repeated interval laparoscopic HIPEC	To examine the rate of conversion to resectability with repeated interval laparoscopic HIPEC as defined by the Phase II trial published by Badgwell et al.	2 years
To quantitatively assess peritoneal cancer index (PCI) change with repeated interval laparoscopic HIPEC.	To quantitatively assess peritoneal cancer index (PCI) change with repeated interval laparoscopic HIPEC.	2 years
Overall Survival Rate	To examine overall survival from diagnosis of metastatic disease. Given the potential for longer survival with repeated interval laparoscopic HIPEC compared to systemic chemotherapy alone, this metric will be assessed. In addition, in (+)PD-L1 patients, survival data in this population undergoing repeated interval laparoscopic HIPEC and systemic PD-1 inhibition is unknown.	2 years
Perioperative morbidity at 30 days	To assess perioperative morbidity at 30 days.	30 days
Perioperative mortality at 30 days	To assess perioperative mortality at 30 days.	30 days

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Ardaman Shergill, University Of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Abdominal Neoplasms; Stomach Neoplasms; Carcinoma; Peritoneal Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: IRB19-0160

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No