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Injection of Bromelain and Acetylcysteine in Combination Into Recurrent Mucinous Tumour or Pseudomyxoma Peritonei

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03976973
Recruitment Status : Not yet recruiting
First Posted : June 6, 2019
Last Update Posted : March 9, 2020
Sponsor:
Collaborators:
Mercy Medical Center
Wake Forest University Health Sciences
St George Hospital, Australia
Memorial Sloan Kettering Cancer Center
Catharina Ziekenhuis Eindhoven
Hospices Civils de Lyon
Information provided by (Responsible Party):
David Morris, Mucpharm Pty Ltd

Brief Summary:

This study involves 100 patients with mucinous peritoneal tumour, including pseudomyxoma peritonei (PMP), that are not suitable for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) or other potentially beneficial surgery.

The combination drug treatment of Bromelain and Acetylcysteine (BromAc) will be administered directly into the tumour or peritoneal cavity via percutaneous drain and allowed to dwell for 24 hours. The tumour will then be drained and a repeat treatment will be considered.

An interventional radiologist will insert a percutaneous drain. The drain will remain in situ for the treatment period. The aspiration (drainage) and repeat drug treatments will be delivered via this drain. The dose of the drug is dependent on the calculated tumour dimensions and volume outlined in the protocol.

The expectation is that the drug combination will dissolve the tumour, allowing it to be removed. Remaining mucinous tumour that is unable to be drained will be considered for repeat drug treatments.


Condition or disease Intervention/treatment Phase
Pseudomyxoma Peritonei Peritoneal Cancer Mucinous Adenocarcinoma Mucinous Tumor Drug: Bromelain, Stem Drug: Acetylcysteine Procedure: Interventional radiology insertion of drain Diagnostic Test: Pathology: blood testing during intervention Other: Routine follow up Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Injection of Bromelain and Acetylcysteine in Combination Into Recurrent Mucinous Tumour or Pseudomyxoma Peritonei
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : November 2021


Arm Intervention/treatment
Experimental: Intervention
Patients with inoperable pseudomyxoma peritonei or peritoneal mucinous tumour that meet the entry criteria and consent to the intervention will receive intratumoural or intraperitoneal treatment/s with the combination experimental drug treatment BromAc. The drug will be injected directly into the tumour or free intraperitoneally via a percutaneously radiologically placed drain.
Drug: Bromelain, Stem
Intratumoural injections of Bromelain 15-45mg (concentration 600ug/ml) or intraperitoneal injections of Bromelain 60mg will be administered via a radiologically placed drain in combination with Acetylcysteine in 0.9% sodium chloride (normal saline).
Other Name: Bromelain

Drug: Acetylcysteine
Intratumoural injections of Acetylcysteine 1g or intraperitoneal injections of Acetylcysteine 2g will be administered via a radiologically drain in combination with Bromelain in 0.9% sodium chloride (normal saline).
Other Names:
  • N-acetylcysteine
  • Acetadote

Procedure: Interventional radiology insertion of drain
Under radiological guidance (CT), a needle, wire, dilator will be placed directly into the tumour then a large pigtail drain (i.e. 10Fg) will be placed into the tumour by an experienced, interventional radiologist, under standard procedures.

Diagnostic Test: Pathology: blood testing during intervention
Blood tests are taken 3 hours after each drug intervention then 24 hours following the last drug intervention to assess for short-term systemic side effects and measure pharmacokinetics of bromelain and acetylcysteine.

Other: Routine follow up
Patients will have outpatient reviews at 1 week and 1, 3, 6, 9 and 12 months post drug intervention. Blood tests will be performed at 1 week and 1, 3, 6, 9 and 12 months after the drug intervention to assess for short and long term systemic side effects. At 1, 3, 6, 9 and 12 months post drug intervention, a CT-scan is part of the study protocol to assess for response and progression of disease.




Primary Outcome Measures :
  1. Tumour response [ Time Frame: 1 month ]
    Tumour changes following BromAc combination treatment. Efficacy will be measured by the volume of fluid aspirated from the drain (dissolved tumour). The treatment will be seen effective if >25% 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.

  2. Incidence of Treatment-Emergent Adverse Events (Pathology) [Safety and Tolerability] [ Time Frame: 1 month ]
    Reported as any untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered BromAc, and judged possibly, probably, or definitely related to treatment


Secondary Outcome Measures :
  1. Progression free survival post treatment [ Time Frame: 1, 3, 6, 9 and 12 months ]
    Time to progression of the treated area based on repeat CT scanning where RECIST v1.1 will be used where possible. The follow up scan will be compared to the 1 month post treatment scan where dimensions and volume will be calculated by an experienced radiologist.

  2. 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)'. [ Time Frame: Baseline, then at 1 month, 3 months, 9 months and 12 months ]

    The EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire Core - C30) is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / Quality of Life (QoL) scale, and six single items.

    The global health status / Quality of Life scale has scores from 1 (very poor) to 7 (excellent) and the others from 1 (not at all) to 4 (very much) where 4 is the worst score. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.


  3. 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) [ Time Frame: Baseline, then at 1 month, 3 months, 9 months and 12 months ]
    The symptom scores (Fatigue, Nausea and vomiting, Pain …), with scores from 1 (not at all) to 4 (very much), where 4 is the worst score, will be evaluated by the use of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Colorectal Cancer (EORTC-QLQ-CR29). The trend of each category of outcome measures given by the EORTC-QLQ-CR29 in four groups of patients: tumour on the right and transverse part of the colon; tumour on the left part of the colon; rectal tumour; metastatic colorectal cancer.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Mucinous tumour or pseudomyxoma peritonei (target lesion or free intraperitoneal) as identified on prior histology or radiology
  • Considered at high risk for repeat surgery, or do not wish to explore repeat surgery and consent to the trial procedures
  • Considered suitable for the trial based on multidisciplinary team meeting review

Exclusion Criteria:

  • Non-mucinous tumour recurrences (hard tumour)
  • Suspected fistulation of the tumour into the gastrointestinal tract, invading or abutting major vessel or other area of concern (fistulation into bladder or vaginal cuff is not an exclusion for treatment)
  • Known allergy (anaphylaxis) to pineapples, papain, bromeliads, sulphur, eggs or Acetylcysteine
  • Coagulation disorders of any kind or are on anticoagulant or anti-platelet therapy that cannot be managed or withheld for the treatment period
  • Signs of an infected tumour (pus on aspiration or indicated on blood test)
  • Eastern Cooperative Oncology Group (ECOG) score >2
  • Other serious co-morbidities where inclusion in the trial will subject the patient to a higher risk of adverse events
  • Unable to provide fully informed and educated consent or are unable to comply with the standard follow up procedures of a clinical trial
  • Considered by the interventional radiologist to have a tumour that is not percutaneously accessible

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03976973


Contacts
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Contact: David L Morris, MD, PhD +61291132070 david.morris@unsw.edu.au
Contact: Sarah J Valle, BN +61291132070 sarah.valle@mucpharm.com

Sponsors and Collaborators
David Morris
Mercy Medical Center
Wake Forest University Health Sciences
St George Hospital, Australia
Memorial Sloan Kettering Cancer Center
Catharina Ziekenhuis Eindhoven
Hospices Civils de Lyon
Investigators
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Principal Investigator: David L Morris, MD, PhD St George Hospital
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Responsible Party: David Morris, Professor of Surgery, Director, Mucpharm Pty Ltd
ClinicalTrials.gov Identifier: NCT03976973    
Other Study ID Numbers: BRACIS-2
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: March 9, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Pseudomyxoma Peritonei
Adenocarcinoma, Mucinous
Cystadenocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes