Intraperitoneal LSTA1 in CRS-HIPEC

A Phase I Trial of Intraperitoneal LSTA1 in Patients Undergoing Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy

This Study is designed to test an investigational product (IP) called LSTA1 (Study drug). LSTA1 is a drug designed to improve the delivery of anti-cancer treatments, such as chemotherapy. Improved delivery of chemotherapy may result in improved anti-cancer effects when given with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases. Participants will be randomized to receive LSTA1 with HIPEC or HIPEC alone (without LSTA1) at the time of surgery.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Ovarian Carcinoma; Peritoneal Metastases; Appendix Cancer
• Intervention / Treatment: Drug: CRS-HIPEC + LSTA1; Procedure: CRS-HIPEC alone

Detailed Description

Given the high recurrence and disease-related mortality in patients with peritoneal metastases from appendiceal, colorectal, and ovarian cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), use of an agent to improve operative tumor delivery of co-administered anticancer drugs during HIPEC would potentially have significant impact on oncologic outcomes.

Safety of LSTA1 has been demonstrated in the context of metastatic pancreatic cancer when administered intravenously with cytotoxic chemotherapy, but the investigators wish to determine its safety and potential efficacy when administered intraperitoneally with HIPEC in patients with peritoneal metastases from appendiceal, colorectal, and ovarian cancer.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joel Baumgartner; Phone Number: (858) 246-0581; Email: J1baumgartner@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California San Diego
      • Contact: John Bienvenida; Phone Number: 858-822-4907; Email: jbienvenida@health.ucsd.edu
      • Principal Investigator: Joel Baumgartner

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Participants must have histologically confirmed non-mucinous (< 50% mucin) colorectal, ovarian, or appendiceal carcinoma with peritoneal metastases who are candidates for (cytoreductive surgery and CRS-HIPEC and have at least one peritoneal tumor nodule > 5 mm (as determined by routine preoperative imaging and confirmed by intraoperative assessment).
4. Eligible and intended to undergo CRS-HIPEC per the investigators. This includes assessment of axial imaging (computed tomography, magnetic resonance imaging, positron emission tomography scan) of chest, abdomen, and pelvis, within 30 days of screening, which reveals peritoneal metastases amenable to complete cytoreduction per the investigators (i.e. limited small bowel/mesenteric metastases), lack of extra-peritoneal metastases (including intra-hepatic and pulmonary metastases), and lack of untreated biliary, gastrointestinal, and urologic obstruction.
5. Age ≥ 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status < 2.
7. Women of child-bearing potential with negative pregnancy test prior to undergoing CRS-HIPEC.
8. Adequate contraception for participants able to cause a pregnancy:

Exclusion Criteria:

1. Participants who do not receive HIPEC at the time of CRS.
2. Any major surgery or irradiation within 30 days prior to prior to planned date of CRS-HIPEC.
3. Active infection (viral, fungal, or bacterial) requiring systemic therapy.
4. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), tuberculosis, or human immunodeficiency virus (HIV) infection.
5. History of allogeneic tissue/solid organ transplant.
6. History or clinical evidence of central nervous system (CNS) metastases without exceptions
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to LSTA1 or other agents used in the study, including those discovered by other ongoing studies of LSTA1 or other agents used in the study.
8. Existing venous thromboembolism at the time of CRS-HIPEC.

9. Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to undergo CRS-HIPEC and receive study treatment. This includes, but is not limited to the following laboratory values and other parameters within 30 days prior to planned date of CRS-HIPEC:

   1. Platelets < 100,000/mm3
   2. White blood cell count < 3000/ mm3
   3. Absolute neutrophil count < 1,500/mm3
   4. Serum albumin < 2.5 g/L
   5. Alanine transaminase (ALT) and aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN) in the absence of liver metastases or > 5 x ULN in the presence of liver metastases
   6. Bilirubin > 1.5 x ULN
   7. Glomerular Filtration Rate (per Modification of Diet in Renal Disease equation) < 30 mL/min
   8. Hemoglobin < 9.0 g/dL (drawn 24 hours after a transfusion, if relevant)
   9. International normalised ratio (INR) > 2.0 (for patients not receiving therapeutic anticoagulation)
   10. Adequate respiratory and cardiac function (PaO2 ≥ 60 mm Hg or oxygen saturation ≥ 92% on room air, and 12-lead electrocardiogram (ECG) with normal tracing or QT interval < 470 ms)
10. Participants who are pregnant or nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CRS-HIPEC + LSTA1; Experimental Arm	Drug: CRS-HIPEC + LSTA1; LSTA1 given with hyperthermic intraperitoneal chemotherapy (HIPEC) at time of cytoreductive surgery (CRS)
Active Comparator: CRS-HIPEC alone; Control Arm	Procedure: CRS-HIPEC alone; Hyperthermic intraperitoneal chemotherapy (HIPEC) alone (without LSTA1) at time of cytoreductive surgery (CRS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events of interest (AE-I)	The proportion of subjects experiencing an inpatient adverse event of interest (AE-I; gastrointestinal fistula/leak, neutropenia, intra-abdominal abscess, venous thromboembolism, mortality)	postoperatively from the date of CRS-HIPEC to date of discharge (typically 1-2 weeks)
Drug concentration in tumor	Total drug content in tumor, divided by total tumor mass	at time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival and Overall Survival	Time (in months) from randomization to time of progression or death due to any cause, whichever occurs first (PFS), or to time of death due to any cause (OS).	5 years
Adverse Events (AEs)	Incidence of any adverse events (AEs) by grade and system organ class using CTCAE v5.0 up to 30 days from the date of CRS-HIPEC.	30 Days

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Joel Baumgartner, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Cecal Diseases; Cecal Neoplasms; Appendiceal Neoplasms
• Other Study ID Numbers: UCSD 807804

Drug and device information, study documents

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