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Trial registered on ANZCTR


Registration number
ACTRN12614000612617
Ethics application status
Approved
Date submitted
22/05/2014
Date registered
6/06/2014
Date last updated
23/08/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I/II Study of the Tolerability, Safety and Pharmacokinetics of Oral Monepantel (MPL) in Individuals with Treatment-Refractory Solid Tumours.
Scientific title
A Phase I/II Study of the Tolerability, Safety and Pharmacokinetics of Oral Monepantel (MPL) in Individuals with Treatment-Refractory Solid Tumours.
Secondary ID [1] 284613 0
LL1
Universal Trial Number (UTN)
U1111-1156-8971
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 291918 0
Condition category
Condition code
Cancer 292271 292271 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Oral Monepantel (MPL) once daily for 28 days in escalating dose cohorts. Starting dose for the first cohort is 5 mg/kg bw, with planned dose escalations to 25 mg/kg bw and 62.5 mg/kg bw in subsequent dose cohorts. An additional dose cohort may be enrolled, dependent emerging results from earlier cohorts.

Study participants will also be required to complete a dosing diary card for each dose of study medication, and return any unused medication at the next clinic visit.

Following completion of the 28 day treatment period study participants may opt to continue extension period, during which time they will continue to receive access to study medication. During the extension period, participants will be required to attend monthly outpatient visits for medical review, collection of blood samples, measurements of vital signs etc. At each monthly visit you will be required to return any unused study medication, and will be dispensed with enough study medication for one month of daily home dosing. Participants will receive standard medical care from their usual treating doctors/team. Participation in the Extension Period may occur indefinitely, or until the participant withdraws or experiences disease progression.
Intervention code [1] 289389 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292135 0
Describe the safety, tolerability, dose-limiting toxicities, and maximum-tolerated dose (MTD) of MPL in humans with treatment-refractory solid tumours.

All adverse events will be assessed for dose limiting toxicity potential using NCI Common Terminology Criteria for Adverse Events (CTCAE v.4). Regular vital signs and clinical laboratory tests will be conducted throughout study participation.
Timepoint [1] 292135 0
Over 28 days of daily dosing with MPL.
Primary outcome [2] 292136 0
Describe the multiple-dose pharmacokinetics of MPL in participants with treatment-refractory solid tumours.

Serial blood samples for pharmacokinetic analysis will be collected after commencement of study drug on Day 1, with regular samples being collected over the whole treatment period. Blood samples will be analysed for concentration of MPL and its metabolites. Spot urine samples over the course of the treatment period will be collected to provide information on MPL accumulation.
Timepoint [2] 292136 0
During 28 days of daily dosing with MPL.

Multiple blood samples will be taken following drug administration at Day 1 during an overnight stay period. Blood samples will also be collected daily to Day 7, then weekly for the remainder of the treatment period. Participants continuing in the Extension Period will provide once monthly blood samples.

Blood samples will continue to be collected monthly until the participant discontinues in the Extension Period.
Secondary outcome [1] 308273 0
Evaluate evidence for anti-cancer activity of MPL in humans.

Evidence for anti-cancer activitiy will be evaluated from the results of PET/CT scans reported according to RECIST criteria. CT scans and time to disease progresion will alo be evaluated. Biopsy tissue and/or ascitic fluid (additional optional consent required) will be collected for exploratory assays assessing cell proliferation and apoptosis.
Timepoint [1] 308273 0
Following 28 days of daily dosing with MPL.

Eligibility
Key inclusion criteria
Male or female patients with progressing and unresectable tumours in whom all standard treatments have been exhausted or have been contraindicated.
Life expectancy of at least 3 months, in the opinion of the Investigator.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Recent treatment (i.e. within 14 days of screening) with any systemic anticancer therapy.

Participants for whom standard therapy exists, and in the view of the Invesigator, is appropriate.

Unresolved recovery from recent major surgery, or unresolved toxicity from recent radiotherapy.

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Sufficient data was obtained to permit proceeding to Phase II study, i.e. a safe and active dose. The study was also terminated to permit reformulation of study drug to a more palatable formulation.
Date of first participant enrolment
Anticipated
17/06/2014
Actual
Date of last participant enrolment
Anticipated
Actual
15/05/2015
Date of last data collection
Anticipated
Actual
1/06/2015
Sample size
Target
9
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 2466 0
The Royal Adelaide Hospital - Adelaide

Funding & Sponsors
Funding source category [1] 289240 0
Commercial sector/Industry
Name [1] 289240 0
PharmAust Limited
Country [1] 289240 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
PharmAust Limited
Address
Suite 7, The Avenue
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 287914 0
None
Name [1] 287914 0
Address [1] 287914 0
Country [1] 287914 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291010 0
Royal Adelaide Hospital - Research Ethics Committee
Ethics committee address [1] 291010 0
Royal Adelaide Hospital
North Terrace
SA 5000
Ethics committee country [1] 291010 0
Australia
Date submitted for ethics approval [1] 291010 0
05/02/2014
Approval date [1] 291010 0
10/04/2014
Ethics approval number [1] 291010 0
HREC/14/RAH/39

Summary
Brief summary
This study is evaluating the tolerability, safety and pharmacokinetics of Oral Monepantel (MPL) in patients with advanced solid tumours that do not respond to standard treatments.

Who is it for?
You may be eligible to joint this study if you have progressing and unresectable tumours, and have a life expectancy of greater than three months. All standard treatments need to have been exhausted or are contraindicated.

Study details
Following enrolment in the study, participants will receive an oral liquid dose of MPL once daily for 28 days. The first three participants enrolled in the study will receive 5mg /kg of body weight in each dose. If there are no toxicities or safety events observed in the first three participants, another three participants will be enrolled and receive 25 mg/kg of body weight in each dose. An additional three participants will be enrolled at 62.5 mg/kg body weight per dose if no toxicities/safety events are observed at 25 mg /kg body weight. If dose-limiting toxicities are observed at any dose level, an additional three participants will be enrolled at the same dose level, before the next dose level is initiated.

This study design aims to determine whether there is a safe maximum dose that can be provided to patients with this condition.

The results of the study will contribute towards the development of MPL as an anticancer treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48458 0
Prof Michael Brown
Address 48458 0
Director, Cancer Clinical Trials Unit
Royal Adelaide Hospital
North Terrace
Adelaide
SA 5000
Country 48458 0
Australia
Phone 48458 0
+61 8 8222 4157
Fax 48458 0
Email 48458 0
[email protected]
Contact person for public queries
Name 48459 0
Louise Pirc
Address 48459 0
CMAX
Level 5, Royal Adelaide Hospital
North Terrace
SA 5000
Country 48459 0
Australia
Phone 48459 0
+61 8 8222 3923
Fax 48459 0
Email 48459 0
[email protected]
Contact person for scientific queries
Name 48460 0
Roger Aston
Address 48460 0
PharmAust Ltd
Suite 7, The Avenue
Nedlands
WA 6007
Country 48460 0
Australia
Phone 48460 0
+61 402 762 204
Fax 48460 0
Email 48460 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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