Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000268549p
Ethics application status
Submitted, not yet approved
Date submitted
15/12/2023
Date registered
15/03/2024
Date last updated
8/09/2024
Date data sharing statement initially provided
15/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
LEPO: A phase 1 study of Leptospermum petersonii extract for patients with mesothelioma
Scientific title
LEPO: A phase 1 study of Leptospermum petersonii extract for patients with mesothelioma
Secondary ID [1] 311168 0
ADRI002
Universal Trial Number (UTN)
Trial acronym
LEPO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mesothelioma 332342 0
Condition category
Condition code
Cancer 329052 329052 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Test drug: QV0 containing leptospermum petersonii extract
- the dose administered, level 1: 150mg per day; level 2: 300mg per day; level 3: 600mg per day; level 4: 1200mg per day. e.g. First 5 participants receive level 1 and once their 6 weeks of treatment are completed the next 5 participants complete level 2, etc.
- the duration of administration, oral QV0 capsules daily every 3 weeks (one cycle) for 6 weeks
- the mode of administration, oral capsule. laboratory test will be used to monitor adherence to the intervention.
Intervention code [1] 327612 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336885 0
To determine the maximum tolerated dose of QV0 as monotherapy (in dose escalation) in patients with mesothelioma
Timepoint [1] 336885 0
History taking and medical examination on Cycle 1 day 1, day 8 and day 1 of subsequent cycles.
Bloods on Cycle 1 day 1, day 2 and day 8 and day 1 of subsequent cycles.
Urine on Cycle 1 day 1, day 2 and day 1 of subsequent cycles
ECG on Cycle 1 day 1, day 8 and day 1 of cycle 2 and 3.
Primary outcome [2] 336886 0
To identify dose limiting toxicities and safety profile of QV0 as mono therapy (in dose escalation) and in combination with standard of care treatment (in dose expansion) in mesothelioma patients
Timepoint [2] 336886 0
History taking and medical examination on Cycle 1 day 1, day 8 and day 1 of subsequent cycles.
Bloods on Cycle 1 day 1, day 2 and day 8 and day 1 of subsequent cycles.
Urine on Cycle 1 day 1, day 2 and day 1 of subsequent cycles
ECG on Cycle 1 day 1, day 8 and day 1 of cycle 2 and 3.
Primary outcome [3] 336887 0
To establish the pharmacokinetic profile of derivatives (AUC, Cmax, Tmax, T1/2) of QV0 in mesothelioma patients taking QV0 as mono therapy
Timepoint [3] 336887 0
Bloods: 0.5, 1, 3, and 24 hours after the first dose
Urine: 1, 3 and 24 hours after the first dose
Secondary outcome [1] 430042 0
To determine preliminary efficacy (response rate) of QV0 at the estimated MTD as mono therapy and in combination with standard of care treatment
Timepoint [1] 430042 0
Pre cycle 3 and then as per investigator

Eligibility
Key inclusion criteria
Inclusion criteria must be met at the time of study screening.
• Histological or cytological documentation of mesothelioma
• Radiological progression following treatment with standard lines of therapy
OR if a patient is not a candidate for standard therapy or does not wish to have standard therapy in the dose escalation phase
OR
Patients suitable for standard of care chemotherapy-based therapy or immunotherapy treatment in the dose expansion phase
• Patient must have at least one measurable lesion according to the RECIST criteria version 1.1 for peritoneal mesothelioma and modified RECIST criteria for pleural mesothelioma
• Male or female patients, 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 2.
• Life expectancy of at least 3 months.
• Women of childbearing potential (age 18 – 55 years old) and men must agree to use adequate contraception from the time of signing of the informed consent form until at least 3 months after the last study drug administration. The investigator or a designated associate is requested to advise the subject on how to achieve adequate birth control. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory testing conducted within 14 days of starting to study treatment:
o Total bilirubin less than or equal to 1.5 x the upper limit of normal (ULN)
o Alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN
o Serum creatinine less than or equal to 1.5 x ULN or Glomerular filtration rate (GFR) greater than or equal to 60 ml/min/m2
o INR/PTT less than or equal to 1.5 x ULN (patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists.
o Platelet count greater than or equal to 100 x 109/L
o Haemoglobin (Hb) greater than or equal to 90g/L
o Absolute Neutrophil count (ANC) greater than or equal to 1.5 x 109/L
• Sufficient archival tissue at screening (paraffin block or at least 15 slides)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous or concurrent cancer that is distinct in primary site or histology from mesothelioma within 3 years from the date of screening EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumours (Ta, Tis and T1).
• Herbal supplements (such as St John’s Wort), nutritional supplements with 10 day washout period
• Major surgical procedures in the last four weeks.
• Pregnancy or breast-feeding.
• Congestive heart failure, New York Heart Association (NYHA) class 2.
• Unstable angina (angina at rest) or new-onset angina ( 3 months). Myocardial infarction less than 6 months before eligibility screening.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
• Uncontrolled hypertension (Systolic blood pressure > 150 mmHg or diastolic pressure > 90 mm Hg despite optimal medical management).
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including Transient Ischemic Attacks), deep vein thrombosis or pulmonary embolism within 3 months before the screening radiographic studies.
• Ongoing infection > grade 2 NCI-CTCAE version 4.0
• Symptomatic brain metastasis(es)
• Patients with a history of bleeding diathesis: Any haemorrhage or bleeding event at CTCAE Grade 3 within 4 weeks of the proposed start of study medication.
• Substance abuse, medical, psychological or social conditions that in the opinion of the investigator may interfere with the patient’s participation in the study or evaluation of the study results.
• Known hypersensitivity to any of the excipients of QV0
• Any gastrointestinal conditions that may prevent or interfere with the oral administration and gastrointestinal absorption of QV0
• Any medical condition that is unstable or could jeopardize the safety of the patient and his/her compliance in the study.
• Unresolved toxicity higher than NCI-CTCAE (version 5.0) Grade 2 attributed to any prior therapy/procedure excluding alopecia.
• Standard exclusionary conditions associated with standard of care treatment in the dose escalation phase, such as significant autoimmune diseases for immunotherapy or significant peripheral neuropathy and ototoxicity for cisplatin-based therapy.

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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2025
Actual
Date of last participant enrolment
Anticipated
1/05/2027
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315745 0
Government body
Name [1] 315745 0
Insurance and Care NSW
Country [1] 315745 0
Australia
Primary sponsor type
Other
Name
ADDRI
Address
3 Hospital Rd, Concord
Country
Australia
Secondary sponsor category [1] 317859 0
None
Name [1] 317859 0
Address [1] 317859 0
Country [1] 317859 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314337 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 314337 0
Ethics committee country [1] 314337 0
Australia
Date submitted for ethics approval [1] 314337 0
10/10/2023
Approval date [1] 314337 0
Ethics approval number [1] 314337 0

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

Contacts
Principal investigator
Name 131230 0
A/Prof Steven Kao
Address 131230 0
Asbestos and Dust Disease Research Institute, Gate 3, Hospital Rd. Concord, NSW, 2139
Country 131230 0
Australia
Phone 131230 0
+61 02 97679860
Fax 131230 0
Email 131230 0
[email protected]
Contact person for public queries
Name 131231 0
Steven Kao
Address 131231 0
Asbestos and Dust Disease Research Institute, Gate 3, Hospital Rd. Concord, NSW, 2139
Country 131231 0
Australia
Phone 131231 0
+61 02 97679860
Fax 131231 0
Email 131231 0
[email protected]
Contact person for scientific queries
Name 131232 0
Huaikai Shi
Address 131232 0
Asbestos and Dust Disease Research Institute, Gate 3, Hospital Rd. Concord, NSW, 2139
Country 131232 0
Australia
Phone 131232 0
+61 425615286
Fax 131232 0
Email 131232 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?

No Supporting Document Provided



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.