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Trial registered on ANZCTR


Registration number
ACTRN12619001282178
Ethics application status
Approved
Date submitted
16/07/2019
Date registered
17/09/2019
Date last updated
19/09/2019
Date data sharing statement initially provided
17/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A multi-centre, randomised, phase IV study to compare the efficacy of oxycodone/naloxone verses oxycodone prolonged release tablets in patients with advanced cancer
Scientific title
A multi-centre, randomised, phase IV study to compare the efficacy of oxycodone/naloxone verses oxycodone prolonged release tablets in patients with advanced cancer
Secondary ID [1] 298352 0
nil known
Universal Trial Number (UTN)
Trial acronym
ENHANCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cancer related pain 313007 0
Condition category
Condition code
Cancer 311512 311512 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study drugs used in this trial are oxycodone/naloxone prolonged release (OXN PR) and oxycodone prolonged release tablets (Oxy PR). The trial is designed to demonstrate equivalence between OXN PR and Oxy PR with respect to analgesic efficacy based on average pain over the last 24 hours as measured by the Brief Pain Inventory – Short Form (BPI-SF) and to demonstrate superiority of constipation management in oxycodone/naloxone prolonged release (OXN PR) compared to oxycodone prolonged release tablets (Oxy PR) amongst cancer patients with pain.
This is a multi-centre, open-label, randomised, phase IV study of oxycodone/naloxone prolonged-release (OXN PR) or oxycodone alone prolonged-release (Oxy PR) in patients with metastatic (Stage IV) solid tumours or haematological malignancies with cancer-related pain. Following randomisation to either ARM 1, oxycodone/naloxone prolonged-release (OXN PR) or ARM 2, oxycodone alone prolonged-release (Oxy PR), patients will enter the main study phase for 5 weeks. During the first week, the dose of oxycodone alone prolonged-release (Oxy PR) or oxycodone/naloxone prolonged-release (OXN PR) will be titrated to analgesic effect. The dose range is Oxy PR 20-160 mg per day or OXN PR 20/10 - 160/180 mg per day either as first prolonged release opioid or switched from a different opioid, as determined by the investigator. The investigator together with the participant will subjectively determine that the analgesic effect has been reached in week 1 of the study. Week 1 is followed by a 4-week assessment period with oxycodone alone prolonged-release (Oxy PR) or oxycodone/naloxone prolonged-release (OXN PR) doses adjusted only as necessary for ongoing analgesic titration at clinician discretion. At the end of the main study phase ( week 5) patients will move into the continuation phase. In the continuation study phase, patients originally in ARM 2 (Oxy PR) of the main study phase may be switched to receive ARM 1 treatment (OXN PR), and patients originally in ARM 1 (OXN PR) of the main study phase may be switched to receive ARM 2 treatment (Oxy PR) provided they are still able to swallow study medication, able to complete PRO tools and willing to switch medications. The continuation study will run for a further 6 weeks, with scheduled assessments occurring at 2-week intervals. Overall duration of administration is 11 weeks. Adherence of drug administration will be recorded at scheduled assessments. A trial drug medication list will be completed by recording number of pills dispensed and number of pills returned. It is anticipated it will take approximately 12 months to accrue 96 patients. The duration of the study will be 18 months. The administration of both medications will be the same, with instructions according to product information: Tablets will be taken every 12 hours regularly (twice daily), differing doses as prescribed per patient.
Intervention code [1] 314593 0
Treatment: Drugs
Comparator / control treatment
The main comparator for this study will be patients in ARM 2 of the study. These patients will be administered Oxycodone prolonged release.
Control group
Active

Outcomes
Primary outcome [1] 320223 0
The primary outcome is to measure average pain over last 24 hours as measured by the BPI-SF at each time point taken over a 5-week period.

Timepoint [1] 320223 0
The primary time point is 5 weeks. The outcome will be assessed at Week 0, 1, 3 and 5.
Secondary outcome [1] 370926 0
Degree of constipation as measured by the Bowel Function Index

Timepoint [1] 370926 0
Measured every two weeks for 11 weeks. week 0, 1, 3, 5, 7, 9 and 11.
Secondary outcome [2] 373409 0
Quality of life, including nausea, vomiting, diarrhoea, appetite, functional activity, breathlessness, insomnia, fatigue, mood, memory, as measured by the EORTC-QLQ-C30
Timepoint [2] 373409 0
Measured every two weeks for 11 weeks. Week 0, 1, 3, 5, 7,9 and 11.
Secondary outcome [3] 373410 0
To measure the total daily dose of rescue analgesia as measured by patient medication diary
Timepoint [3] 373410 0
Every two weeks for 11 weeks. Week 0, 1, 3, 5, 7,9 and 11.
Secondary outcome [4] 373411 0
To measure total dose of study medication as measured by pill count
Timepoint [4] 373411 0
Every two weeks commencing at week 1, followed by week 3, 5, 7, 9 and 11
Secondary outcome [5] 373412 0
To measure total laxative dose over a 5-week period
Timepoint [5] 373412 0
Every two weeks for 11 weeks. Commencing at Week 0, Followed by 1,3 ,5, 7, 9 and 11

Eligibility
Key inclusion criteria
1. Patient has provided written informed consent
2. Aged 18 years or older at the time of informed consent
3. Metastatic (Stage IV) solid tumour or haematological malignancy
4. Patient has moderate to severe cancer-related pain defined as a numeric pain rating score of greater than or equal to 4 requiring commencement of Oxy PR 20-160mg per day or OXN PR 20/10 – 160/80mg per day either as first prolonged release opioid or switched from a different opioid, as determined by the investigator
5. Patients must have adequate organ function within 14 days of randomisation:
Defined by:
- Serum alanine aminotransferase less than 2.5 x upper limit of normal (ULN) and/or serum bilirubin less than 2.5 x ULN
- Serum albumin greater than or equal to 20g/L
- Estimated Creatinine clearance greater than or equal to 50mL/min (using MDRD calculation)
6. Australia Modified Karnofsky Performance Status (AKPS) greater than or equal to 50
7. Able to swallow oral medications
8. Able to complete study assessments
9. Has a life expectancy of at least 12 weeks
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with known liver metastasis
2. Clinically significant gastrointestinal disease including inflammatory bowel disease, intestinal obstruction or pseudo-obstruction, active diverticular disease, gastrointestinal haemorrhage, history of bowel perforation, history of ischaemic colitis
3. New chemotherapy or immunotherapy treatment starting within 14 days prior to randomisation
4. Radiotherapy to any abdominal area or site of pain within 4 weeks of randomisation
5. Enrolment on another clinical trial with an investigational agent for pain within 30 days of randomisation. (Enrolment in other non-pain investigational studies during this study is permitted, including chemotherapy and immunotherapy trials)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified, blocked randomisation list generated by an independent statistician
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
A statistical analysis plan will be written prior to database lock and will provide detailed information on all statistical analyses planned for the trial, including planned methods to deal with missing data. All deviations from the protocol will be detailed and justified.
Baseline patient characteristics will be summarised by treatment arm using descriptive statistics and reported for continuous variables as number of patients, mean, median, minimum and maximum; and for categorical variables as counts and percentages.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13848 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 13849 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [3] 13851 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 14653 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 26611 0
3000 - Melbourne
Recruitment postcode(s) [2] 26612 0
3065 - Fitzroy
Recruitment postcode(s) [3] 26614 0
3084 - Heidelberg
Recruitment postcode(s) [4] 27678 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 302889 0
Commercial sector/Industry
Name [1] 302889 0
Mundipharma
Address [1] 302889 0
88 Phillip St, Sydney NSW 2000
Country [1] 302889 0
Australia
Funding source category [2] 302901 0
Hospital
Name [2] 302901 0
Victorian Comprehensive Cancer Centre
Address [2] 302901 0
305 Grattan St, Melbourne VIC 3000
Country [2] 302901 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street, Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 302855 0
None
Name [1] 302855 0
none
Address [1] 302855 0
none
Country [1] 302855 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303464 0
Peter MacCallum Cancer Centre Human Research Ethics Committee
Ethics committee address [1] 303464 0
305 Grattan Street Melbourne VIC 3000
Ethics committee country [1] 303464 0
Australia
Date submitted for ethics approval [1] 303464 0
27/05/2019
Approval date [1] 303464 0
11/09/2019
Ethics approval number [1] 303464 0

Summary
Brief summary
This study aims to evaluate two pain relief medications, oxycodone/naloxone prolonged-release (OXN PR) and oxycodone alone prolonged-release (Oxy PR). The study will assess how effective these medications are at relieving pain and reducing constipation in patients with advanced cancer.

Who is it for?
You may be eligible to join this study if you are aged 18 years or older and have metastatic cancer (Stage IV) and moderate to severe pain.

Study details
All participants will be randomly assigned (by chance) to either receive a combination drug of oxycodone/naloxone or oxycodone alone. In both groups participants will take two tablets a day, however this dosage may be adjusted if needed by your treating clinician. The study will involve a variety of questionnaires exploring Pain, Quality of life and Bowel movement over a 5 week period initially and if you decide to continue on the study for a total of 11 weeks.

It is hoped this study can provide insight into the clinical effectiveness between the two pain medications and their effect on sustained analgesia and bowel function. This study may provide greater knowledge into how pain is treated in patients with advanced cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 93750 0
Dr Aaron Wong
Address 93750 0
Peter MacCallum Cancer Centre
305 Grattan Street Melbourne VIC 3000
Country 93750 0
Australia
Phone 93750 0
+61 3 85595000
Fax 93750 0
Email 93750 0
Aaron.Wong@petermac.org
Contact person for public queries
Name 93751 0
Dr Aaron Wong
Address 93751 0
Peter MacCallum Cancer Centre
305 Grattan Street Melbourne VIC 3000
Country 93751 0
Australia
Phone 93751 0
+61 3 85595000
Fax 93751 0
Email 93751 0
Aaron.Wong@petermac.org
Contact person for scientific queries
Name 93752 0
Dr Aaron Wong
Address 93752 0
Peter MacCallum Cancer Centre
305 Grattan Street Melbourne VIC 3000
Country 93752 0
Australia
Phone 93752 0
+61 3 85595000
Fax 93752 0
Email 93752 0
Aaron.Wong@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified participant data for all data collected may be considered for sharing with potential collaborators on a case-by-case basis, and as long as it is in line with all agreements signed including patient consent form.
When will data be available (start and end dates)?
From 3 months to up to 3 years following main results publication.
Available to whom?
This will be considered on a case-by-case basis.
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Data can be obtained by emailing the principal investigator. Email address is Aaron.Wong@petermac.org
What supporting documents are/will be available?
No other documents available
Summary results
No Results