BromAc for Recurrent Peritoneal Mucinous Tumour or Pseudomyxoma Peritonei

NCT03976973 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: MUC-ONC-ACP2
• Study Type: interventional
• Target: 62
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Pseudomyxoma Peritonei; Peritoneal Cancer; Mucinous Adenocarcinoma; Mucinous Tumor

Outcome Measures

Primary Outcomes (1)

• Tumour response (objective response rate)

  Tumour changes following BromAc combination treatment compared to baseline. Efficacy will be measured by RECIST v1.1 with the volume of fluid aspirated from the drain (dissolved tumour). The treatment will be seen effective if \>30% of tumour volume is aspirated or there is a \>30% reduction on CT scan post treatment at 1 month compared to the pre-treatment scan. Given the difficulty of assessing soft tumour (cystic/mucinous) response by RECIST, a surrogate assessment of efficacy will be measured (if unable to assess based on RECIST v1.1 criteria) by tumour changes following BromAc combination treatment.

  1 month

Secondary Outcomes (6)

• Progression free survival post treatment

  1 month, 3 months, 6 months, 9 months and 12 months

• Impact of treatment on Quality of Life over time in patients evaluated by the core questionnaire 'European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer (EORTC-QLQ-C30)'.

  Baseline, then at 1 month, 3 months, 6 months, 9 months and 12 months

• Impact of treatment on Quality of Life in colorectal cancer over time by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Colorectal Cancers (EORTC-QLQ-CR29)

  Baseline, then at 1 month, 3 months, 6 months, 9 months and 12 months

• Incidence of Treatment-Emergent Adverse Events (Pathology) [Safety and Tolerability]

  1 month

• Symptomatic response to treatment

  Baseline, 1 week, 1 month, 3 months, 6 months, 9 months and 12 months

Study Arms (1)

Intervention

EXPERIMENTAL

Participants with inoperable pseudomyxoma peritonei or peritoneal mucinous tumour that meet the entry criteria and consent to the intervention will receive intratumoural treatment/s with the combination drug BromAc. The drug product will be injected directly into the tumour via a radiologically placed drain

Drug: Bromelain; Drug: Acetylcysteine; Procedure: Interventional radiology insertion of drain

Interventions

Bromelain DRUG

Intratumoural injections of Bromelain 600ug/ml (maximum dose 90mg daily diluted in 150ml 0.9% NaCl) via a radiologically placed drain in combination with Acetylcysteine in 0.9% sodium chloride (normal saline).

Intervention

Acetylcysteine DRUG

Intratumoural injections of Acetylcysteine 20mg/ml (maximum dose 3g daily diluted in 150ml 0.9% NaCl) via a radiologically placed drain in combination with Bromelain.

Intervention

Interventional radiology insertion of drain PROCEDURE

Under radiological guidance (CT), a needle, wire, dilator will be placed directly into the tumour, then a pigtail drain (10Frg) will be secured into the tumour by an experienced, interventional radiologist, under standard procedures. This drain is utilised as access to the tumour for injections of the investigational drug product BromAc, and subsequent aspirations.

Intervention

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 - 80 years
• Have a mucinous tumour/pseudomyxoma peritonei target lesion with a defined cavity, with the shortest diameter being at least 3 centimeters on radiology, and percutaneously accessible. In the case of a target lesion, tumour located at distant sites (for e.g. pleura) will not exclude a patient from this study and these tumours may be treated, if suitable, under expanded access protocols.
• Are symptomatic or at risk of becoming symptomatic or obstructed imminently, are considered inoperable, at high risk of morbidity, mortality or quality of life decline for repeat surgery, or do not wish to explore repeat surgery
• Are considered suitable for the trial based on a multidisciplinary team meeting case review

You may not qualify if:

• Have a non-mucinous tumour (hard caked tumour) that does not have cystic appearance on radiology. Having a hard tumour appearance in one region does not exclude treatment in another area, provided the appearance is mucinous.
• Have known allergy (anaphylaxis) or allergy to pineapples, papain, bromeliads, sulphur, eggs or Acetylcysteine or any other serious allergy or intolerance to fruits or food products
• Have a coagulation disorder of any kind or are on anticoagulant or anti-platelet therapy that cannot be managed or withheld for the radiology procedure
• Have an infected tumour or ongoing inflammatory process (pus on aspiration at radiology will be a delayed failure) as indicated on baseline blood test
• Eastern Cooperative Oncology Group (ECOG) score \>2
• Have had chemotherapy within the last two weeks, have not had bone marrow recovery from chemotherapy, or had Bevacizumab (Avastin) within the last 4 weeks. A staging baseline scan must be completed prior to considering entry into this study.
• Have previously received BromAc for pseudomyxoma or peritoneal mucinous tumour (see expanded access)
• Pregnant women are excluded from this study because BromAc has unknown but a potential risk for adverse events in nursing infants secondary to treatment of the mother
• Participants with psychiatric illness/social situations that would limit compliance with study requirements
• Are unable to give fully informed and educated consent or are unable to comply with the standard follow up procedures of a clinical trial

Sponsors & Collaborators

• Mucpharm Pty Ltd: lead
• Mercy Medical Center: collaborator
• Wake Forest University Health Sciences: collaborator
• University of Pittsburgh Medical Center: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Hospital Universitario Reina Sofia de Cordoba: collaborator

MeSH Terms

Conditions

Pseudomyxoma Peritonei; Adenocarcinoma, Mucinous; Neoplasms, Cystic, Mucinous, and Serous

Interventions

Bromelains; Acetylcysteine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cysteine Endopeptidases; Cysteine Proteases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Endopeptidases; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Armando Sardi, MD

  Mercy Medical Center, USA

  PRINCIPAL INVESTIGATOR

• Haroon Choudry, MD

  University of Pittsburgh Medical Center, USA

  PRINCIPAL INVESTIGATOR

• Edward Levine, MD

  Wake Forest University Hospital, USA

  PRINCIPAL INVESTIGATOR

• Alvaro Arjona Sanchez, MD

  University Hospital Reina Sofia, Spain

  PRINCIPAL INVESTIGATOR

• Ignace de Hingh, MD

  Eindhoven Catharina Hospital, Netherlands

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David L Morris, MD, PhD

CONTACT

+61291132070; david.morris@unsw.edu.au

Sarah J Valle, BN

CONTACT

+61291132070; sarah@mucpharm.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2019
• First Posted: June 6, 2019
• Study Start: May 1, 2022
• Primary Completion: November 1, 2023
• Study Completion: February 1, 2024
• Last Updated: March 15, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share