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Trial registered on ANZCTR


Registration number
ACTRN12622001288718
Ethics application status
Approved
Date submitted
23/09/2022
Date registered
4/10/2022
Date last updated
4/10/2022
Date data sharing statement initially provided
4/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The safety and tolerability of Annona muricata leaf extract in people living with cancer
Scientific title
The safety and tolerability of Annona muricata leaf extract in people living with cancer
Secondary ID [1] 308018 0
Nil known
Universal Trial Number (UTN)
U1111-1257-3510
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
metastatic or recurrent cancer at stage III or IV 327695 0
Condition category
Condition code
Cancer 324775 324775 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The interventional treatment is an oral capsule containing Annona muricata leaf powder.
Participants (n = 24) will be allocated to one of two groups for 12 weeks. The first 12 participants recruited will receive 530 mg Annona muricata capsule once daily, while the next 12 participants recruited will receive 530 mg Annona muricata capsule twice daily.
Adherence of Annona muricata capsules will be assessed by participant dosing diary and by counting returned medication as compared to the prescribed dose at week 6 and week 12.
Intervention code [1] 324472 0
Treatment: Other
Comparator / control treatment
530 mg Annona muricata twice daily will be the comparator group
Control group
Dose comparison

Outcomes
Primary outcome [1] 332600 0
The side effects of Annona muricata consumption in human were found to be mild, including nausea (13%), heart burn (epigastric pain) (6.6%). In an observational study in human, movement disorders had also been reported.
Safety and tolerability assessed by self-reporting of adverse effects using the participant dosing diary, full clinical assessment including clinical consultation and standard neurological assessment. Standardised mini-mental state examination will be conducted by clinical trial doctor during consultation.
Carcinoembryonic antigen, liver and renal function test and blood glucose will be assessed by whole blood samples. Blood pressure will be assessed by sphygmomanometer.
Timepoint [1] 332600 0
Experience of adverse effect will be monitored and recorded daily in participant dosing diary until week 12 post-intervention commencement. Full clinical assessment will be conducted at baseline, week 3, 6, 9 and 12 post-intervention commencement.
Secondary outcome [1] 414022 0
Inflammation will be assessed by changes in inflammatory markers including serum neutrophil-lymphocyte ratio, C-reactive protein, albumin. These markers will be assessed as a composite secondary outcome.
Timepoint [1] 414022 0
Baseline, week 3, 6, 9 and 12 post-intervention commencement
Secondary outcome [2] 414023 0
Immune function will be assessed by changes in serum CD3, CD4, CD8, CD16/56, CD19 and lymphocyte helper:suppressor ratio via blood test. These markers will be assessed as a composite secondary outcome.
Timepoint [2] 414023 0
Baseline, week 3, 6, 9 and 12 post-intervention commencement
Secondary outcome [3] 414025 0
Quality of life measured by validated questionnaires Functional Assessment of Cancer Therapy-General (FACT-G) version 4 and Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) version 4. Depending on participants’ cancer types, they will be provided with the relevant additional FACT questionnaires specific to their cancer type.
These questionnaires will be assessed as a composite secondary outcome.
Timepoint [3] 414025 0
Baseline, week 3, 6, 9 and 12 post-intervention commencement
Secondary outcome [4] 414026 0
Disease status measured by changes in appropriate biomarkers collected during routine standard care. Imaging including PET-CT, ultrasound and MRI have not been approved by the ethics committee as part of the study protocol separate to their use in routine standard care. As such, during the course of this study, participants may be required to have these investigations conducted.
Timepoint [4] 414026 0
Baseline, week 3, 6, 9 and 12. We expect participants will continue to see their clinical trial doctor after week 12. However, it is not a requirement of the clinical study.

Eligibility
Key inclusion criteria
Inclusion criteria include the diagnosis of metastatic or recurrent cancer at stage III or IV; willing and able to undertake the trial treatment and clinical follow-up; aged greater than or equal to 18 years of age; able to understand the English language in order to give consent and complete questionnaires. Patients who are clinically stable after CNS and/or cranial radiation will be included. This is supported by a lack of evidence of progression by CT scan or MRI or on clinical grounds.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include participants who are actively undergoing (or intend to receive) chemotherapeutic and/or radiotherapeutic treatments; pregnant or breastfeeding; experience dysphagia; Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 3; life expectancy status less than or equal to 12 weeks; full blood counts with white blood cells < 3.0 × 109/L, absolute neutrophil count < 1.5 × 109/L, platelets < 100 × 109/dL; inadequate hepatic (either aspartate transaminase: ALT > 2.5 × upper limit of normal (ULN), or > 5 × ULN for liver metastatic patient or bilirubin > 1.5 × ULN) and/or renal function (< 50 mL/min/1.73 m2); mucositis (disrupted gastrointestinal integrity); grade 2 or higher peripheral neuropathy toxicity; diagnosis of any major psychiatric or neurodegenerative disorders such as Parkinson’s disease or dementia; other major serious medical illness such as poorly controlled diabetes or cardiovascular disease. Participants will also be excluded if they are concurrently taking other T&CM and unable to cease these medicines two weeks before the trial, already enrolled in other cancer treatment trials, plan to undergo major surgery during study, documented allergy to study treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Data integrity will be maintained by regularly reviewing the data for missing data and errors and any inconsistencies will be resolved. Descriptive statistics will be reported for baseline data including participants’ characteristics. For continuous outcome data including serum neutrophil-lymphocyte ration, C-reactive protein, albumin, CD3, CD4, CD16/56, CD19, lymphocyte helper: suppressor ratio, renal and liver function, linear mixed models will be used to examine changes in outcome measures over time. Dose effects will be examined by fitting dosage group as a factor. If there is evidence of an effect of time, post-hoc independent sample t-test will be conducted to compare the mean at follow-up time-points (week 3, 6, 9 and 12) to baseline. If the continuous data is not normally distributed, non-parametric equivalents tests of the above data will be used. For categorical data, proportion and frequencies will be presented in tables. For binary outcomes including whether renal, liver function, full blood count and carcinoembryonic antigen (CEA) falls within or out of the reference range will be assessed by mixed-effect logistic regression. Power calculation is not relevant within the context of a phase I exploratory study.
Statistical data including p-value, 95% confidence interval will be reported. Statistically significant results are considered to have a p-value < 0.05. Data analysis will be conducted using SPSS version 27.0.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2023
Actual
Date of last participant enrolment
Anticipated
1/02/2025
Actual
Date of last data collection
Anticipated
1/08/2025
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 23181 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 38546 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 312281 0
Hospital
Name [1] 312281 0
Concord Cancer Centre
Country [1] 312281 0
Australia
Primary sponsor type
Hospital
Name
Sydney Local Health District, Concord Repatriation General Hospital
Address
Concord Repatriation General hospital, Hospital Rd, Concord NSW 2139
Country
Australia
Secondary sponsor category [1] 313833 0
None
Name [1] 313833 0
Address [1] 313833 0
Country [1] 313833 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311653 0
Bellberry Limited
Ethics committee address [1] 311653 0
Ethics committee country [1] 311653 0
Australia
Date submitted for ethics approval [1] 311653 0
21/01/2021
Approval date [1] 311653 0
19/09/2022
Ethics approval number [1] 311653 0
2022-04-420

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121866 0
A/Prof Philip Beale
Address 121866 0
Ground Floor East, Concord Repatriation General Hospital, 1a Hospital Road, Concord NSW 2137
Country 121866 0
Australia
Phone 121866 0
+61297676354
Fax 121866 0
Email 121866 0
[email protected]
Contact person for public queries
Name 121867 0
Joanna Harnett
Address 121867 0
Rm No N347, Building A15 School of Pharmacy, The University of Sydney Science Road, Camperdown Campus Sydney 2006
Country 121867 0
Australia
Phone 121867 0
+61293517009
Fax 121867 0
Email 121867 0
[email protected]
Contact person for scientific queries
Name 121868 0
Joanna Harnett
Address 121868 0
Rm No N347, Building A15 School of Pharmacy, The University of Sydney Science Road, Camperdown Campus Sydney 2006
Country 121868 0
Australia
Phone 121868 0
+61293517009
Fax 121868 0
Email 121868 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17171Ethical approval    384702-(Uploaded-23-09-2022-11-37-49)-Study-related document.pdf
17176Informed consent form    384702-(Uploaded-23-09-2022-11-49-58)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.