Phase 1/2 Study Evaluating Safety and Potential Efficacy of Allocetra-OTS Via Pressurized Intra-Peritoneal Aerosol Chemotherapy as Add-on to Standard of Care Chemotherapy for Treatment of Peritoneal Metastasis

Study Overview
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Brief Summary
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This is an open-label study to evaluate safety and potential efficacy of Allocetra-OTS in the treatment of patients with peritoneal metastasis as an add-on to the standard of care (SoC) chemotherapy.

Detailed Description
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Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is utilized in patients with malignant dissemination to the peritoneal cavity, for the treatment of peritoneal metastasis that have a high tumor burden or are unresectable, and are unresponsive to systemic therapy. Allocetra-OTS is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state. The study will evaluate the safety and potential efficacy of Allocetra-OTS in the treatment of peritoneal metastasis as an add-on to the standard of care (SoC) chemotherapy. Patients will be treated with escalating doses of Allocetra-OTS as an add-on to the chemotherapy administered via PIPAC, and in addition to systemic chemotherapy.

Official Title
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Phase 1/2 Study Evaluating Safety and Potential Efficacy of Allocetra-OTS Via Pressurized Intra-Peritoneal Aerosol Chemotherapy as Add-on to Standard of Care Chemotherapy for Treatment of Peritoneal Metastasis

Conditions
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Peritoneal Metastases

Intervention / Treatment
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* Drug: Allocetra-OTS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older. Diagnosis of peritoneal metastasis due to any primary tumor by histopathology or cytology Possession of unresectable tumors (not eligible for Cytoreductive Surgery / Hyperthermic Intra-Peritoneal Chemoperfusion CRS/HIPEC). Adequate performance status and surgical risk Adequate hematopoietic, hepatic and renal function Exclusion Criteria: Extraperitoneal disease. Bowel obstruction History of Liver cirrhosis with CHILD PUGH classification of B or C or signs of portal hypertension, portal vein thrombosis. Patient with known New York Heart Association (NYHA) class 3 or 4 symptomatic congestive heart failure, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias. Previous history of organ allograft or stem cell transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohorts 1-2<br>Escalating doses of Allocetra-OTS up to 10 x 10^9 cells. | Drug: Allocetra-OTS<br>* Allocetra-OTS is a cell-based therapy consisting of non-HLA matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state.<br>|
| Experimental: Cohorts 3-4<br>Allocetra-OTS at the maximal tolerated dose. | Drug: Allocetra-OTS<br>* Allocetra-OTS is a cell-based therapy consisting of non-HLA matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of Allocetra-OTS related adverse events (AEs) and serious adverse events (SAEs) | Number and severity of Allocetra-OTS related adverse events (AEs) and serious adverse events (SAEs) during 16-week period starting from the first administration of study treatment. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response Rates (BORR) | Best Overall Response Rates (BORR) will be comprised of clinical, radiological and pathology assessments. | 16 weeks | 
| Change in specific cancer markers | Change in the specific cancer markers (CEA, CA-19-9, CA-125) from baseline to each post-PIPAC assessment. | 16 weeks | 
| Progression-free survival (PFS) | Progression-free survival (PFS) assessed based on imaging data (PET/CT) | 6 months | 
| Overall Survival (OS) | OS up to 12 months from the first administration of study treatment. | 12 months | 
| Change in quality of life | Change in quality of life according to EORTC QLQ-CR29 from screening to 16 weeks. | 16 weeks |