BromAc for Recurrent Peritoneal Mucinous Tumour or Pseudomyxoma Peritonei

Peritoneal Cancer Clinical Trial

Official title: A Phase 2, Multi-centre Study of BromAc for Recurrent Peritoneal Mucinous Tumour or Pseudomyxoma Peritonei

Status Not yet recruiting

Clinical Trial Summary

Pseudomyxoma peritonei (PMP) is an orphan disease, characterized by the progressive accumulation of jelly-like material within the abdomen, which occurs in approximately 2-3 people per million per year. Advanced disease is often the result of tumour perforation and seeding of tumour cells within the peritoneal cavity. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CCRS HIPEC) is the current standard of care for PMP.

An Australian pharmaceutical company is developing BromAc for diseases involving mucin. This drug is composed of Bromelain and Acetylcysteine. During pre-clinical development, the sponsor found that BromAc rapidly dissolved and removed tumour mucin, making it a potent mucolytic. BromAc in combination have the ability, as shown in pre-clinical studies, to remove the mucin protective framework expressed by cancer including mucin (MUC) 1, MUC2, MUC4, MUC5AC and MUC16. The sponsor has shown the mechanism of action of BromAc - to break peptide and glycosidic linkages and disulphide bonds in tumour produced and respiratory mucin. BromAc has been safe in preclinical development with a manageable adverse event profile and preliminary efficacy in a phase 1 study.

This current study will examine the efficacy and safety of applying BromAc directly into recurrent mucinous tumour deposits in patients that are found to be unsuitable for repeat curative intent intervention by CCRS HIPEC.

Clinical Trial Description

Pseudomyxoma peritonei (PMP) is an orphan disease, characterised by the progressive accumulation of jelly-like material within the abdomen, which occurs in approximately 3 people per million per year. Advanced disease is often the result of tumour perforation and seeding of tumour cells within the peritoneal cavity, leading to this syndrome. Multifocal mucin collections are the main cause of morbidity and mortality.

In the past, management of mucinous peritoneal disease involved repeated surgical debulking, with systemic chemotherapy having minimal effect. The combined modality of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CCRS HIPEC) is considered standard of care for peritoneal spread of appendiceal tumours and a treatment option for other mucinous peritoneal tumours. The intention of CCRS HIPEC is cure, however this is dependent on the characteristics and extent of tumour involvement, with the main limitation being amount of disease involving the serosa or mesentery of small bowel.

Mucin produced by tumours is known to be highly resistant to chemotherapy as mucin acts as a tumour coating. Many patients with mucinous tumours or PMP, however, can achieve long-term survival through this therapy although in a significant proportion recurrence following CCRS HIPEC occurs, and repeat interventions for recurrent disease are increasingly complex and may have a negative impact on quality of life, where the risks of the procedure in many cases outweigh the benefits.

BromAc has been safe in preclinical development and in a phase 1 study, patients received up to 60mg/2000mg of BromAc daily for a median of 3.4 days. Serious treatment-related adverse events (12%) were manageable. There were no anaphylactic reactions. An objective response to treatment was seen in 81% of patients. There were no drug-related deaths due to treatment-related adverse events. With a median follow up of 18.2 months, progression was seen in 55% at a median of 5.8 months.

This potential treatment for pseudomyxoma peritonei/appendix mucinous tumours received orphan designation from the (Food and Drug Administration (FDA) (DRU-2018-6644) European Medicines Agency (EMA) (EMA/3/18/2107, EMA/3/18/2113).

The aim of this study is to assess whether the application of BromAc via radiologically placed percutaneous catheters directly into the recurrence dissolves the mucinous tumour, allowing for the dissolved tumour to be drained. The efficacy of this intervention will be assessed via radiological imaging and clinically with the expectation that this combination treatment will result in dissolution and removal of the tumour. The surrogate endpoints used in this study will be radiological response and volume of mucin aspirated. The projected benefits of direct injection of the BromAc include improvement of symptoms of the disease, which frequently include pain, vomiting, inability to maintain adequate oral intake and progressive loss of condition. ;

Related Conditions & MeSH terms

• Adenocarcinoma, Mucinous
• Cystadenocarcinoma
• Mucinous Adenocarcinoma
• Mucinous Tumor
• Peritoneal Cancer
• Pseudomyxoma Peritonei

• NCT number: NCT03976973
• Study type: Interventional
• Source: Mucpharm Pty Ltd
• Contact: David L Morris, MD, PhD
• Phone: +61291132070
• Email: david.morris@unsw.edu.au
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2022
• Completion date: February 2024