Clinical trial NCT06216561: Intraperitoneal LSTA1 in CRS-HIPEC
Official title: A Phase I Trial of Intraperitoneal LSTA1 in Patients Undergoing Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Colorectal Cancer
Ovarian Carcinoma
Appendix Cancer
Peritoneal Metastases
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2024-01-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Unblinded, randomized 2:1 to CRS-HIPEC + LSTA1 vs. CRS-HIPEC alone
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events of interest (AE-I)
timeFrame: postoperatively from the date of CRS-HIPEC to date of discharge (typically 1-2 weeks)
measure: Drug concentration in tumor
timeFrame: at time of surgery
Secondary outcomes:
measure: Progression-Free Survival and Overall Survival
timeFrame: 5 years
measure: Adverse Events (AEs)
timeFrame: 30 Days
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
Study officials:
affiliation: University of California, San Diego
name: Joel Baumgartner
role: PRINCIPAL_INVESTIGATOR
References: