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Trial registered on ANZCTR


Registration number
ACTRN12624001353583
Ethics application status
Approved
Date submitted
11/10/2024
Date registered
11/11/2024
Date last updated
11/11/2024
Date data sharing statement initially provided
11/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Perioperative propranolol and celecoxib (ProCel) in stage III melanoma
Scientific title
Effect of perioperative propranolol and celecoxib (ProCel) on tumoral immune cell populations and proliferative markers in stage III melanoma: a phase II randomised controlled trial
Secondary ID [1] 312172 0
None
Universal Trial Number (UTN)
Trial acronym
ProCel
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma, stage III 333823 0
Condition category
Condition code
Cancer 330495 330495 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to the intervention arm will receive surgery (wide local excision of melanoma or dissection if the metastasis is in a lymph node) plus the ProCel regimen perioperatively, as detailed below.

Oral propranolol
Days 1-2: 20mg twice-daily
Days 3-5: 40mg twice-daily
Day 6 (day of surgery): 60mg twice-daily
Days 7-13: 40mg twice-daily
Days 14-20: 20mg twice-daily

Oral celecoxib
Days 1-20: 200mg twice-daily

Adherence will be assessed by the research team, based on unused tablet count and patient self-report.
Intervention code [1] 328615 0
Treatment: Drugs
Comparator / control treatment
Participants randomised to the control arm will receive standard surgical care without the ProCel regimen.
Control group
Active

Outcomes
Primary outcome [1] 338267 0
Change in tumour immune and proliferative markers (e.g. B2M-c, CD11c, CD14, CD141, CD163, CD16a-c, CD1c-c, CD20, CD27-c, CD31, CD34, CD38, CD39, CD3e, CD4, CD45, CD45RO, CD68, CD8, CollagenIV, FOXP3, GZMB, HLA-A, HLA-DR, HLA-E, ICOS, IDO1, Ki-67, LAG3, MITF-c, MLANA-c, PD-1, PD-L1, PMEL-c, S100B-c, SMA, SOX10-c, TBET-c, TCF7-c, TIM3-c, Vimentin and VISTA) in nodal and/or cutaneous metastatic melanoma (this will be assessed as a composite outcome)
Timepoint [1] 338267 0
Baseline and day 6 after commencing the ProCel regimen
Secondary outcome [1] 435221 0
Safety and tolerability of the ProCel regimen
Timepoint [1] 435221 0
Heart rate at baseline and on days 1-14 after commencing the ProCel regimen; blood pressure at baseline and on day 6 after commencing the ProCel regimen; and dizziness and shortness of breath self-reported on days 6, 20 and 45 after commencing the ProCel regimen
Secondary outcome [2] 435224 0
Change in blood markers of inflammation and immunity
Timepoint [2] 435224 0
Baseline and day 20 after commencing the ProCel regimen
Secondary outcome [3] 435225 0
Quality of life
Timepoint [3] 435225 0
Baseline, day 20 after commencing the ProCel regimen, and 4 months after surgery
Secondary outcome [4] 435228 0
State (modifiable) optimism
Timepoint [4] 435228 0
Baseline, day 20 after commencing the ProCel regimen, and 4 months after surgery
Secondary outcome [5] 441328 0
Perceived stress
Timepoint [5] 441328 0
Baseline, day 20 after commencing the ProCel regimen, and 4 months after surgery
Secondary outcome [6] 441329 0
Evidence of disease recurrence/progression postoperatively
Timepoint [6] 441329 0
4 months after surgery

Eligibility
Key inclusion criteria
Known metastatic cutaneous melanoma in lymph nodes and/or in transit recurrences in skin, measuring at least 0.5cm in largest diameter, appropriate for surgical management and where surgery is expected to render the patient clinically disease free.
Willingness and ability to provide informed consent, and willingness to participate and comply with the study requirements.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to follow up for the duration of the study due to frailty, geographical or social reasons.
Pregnant or lactating (women of childbearing potential must use appropriate contraception).
Known allergy to one or more of the study medications.
Known contraindication to beta-blockers (including hypersensitivity; unstable angina; severe asthma; bronchospasm predisposition; symptomatic hypotension; severe heart failure; moderate to high grade conduction disease; bradycardia less than 50 beats per minute; sick sinus syndrome; severe cardiomegaly; phaeochromocytoma).
Known contraindication to celecoxib (NSAID associated asthma or urticaria; concomitant NSAIDs (excluding low dose aspirin); active peptic ulcer with GI bleed; renal impairment with eGFR less than 30 mL/min).
Patient already taking a beta-blocker, COX2 inhibitor (excluding low dose aspirin i.e. less than or equal to 150 mg daily), or digoxin within one month of study entry.
Immune suppression (including transplant recipients, chronic haematological malignancies, immune-suppressive medications for autoimmune disorders).
Internal malignancy (other than metastatic melanoma) within the past 5 years.
Current use of non-dihydropyridine calcium channel blockers (verapamil or diltiazem) or amiodarone.
Current use of anti-platelets agents (aside from aspirin) i.e. P2Y12 antagonist (clopidogrel, ticagrelor or prasugrel).
Liver failure (cirrhosis).
Treatment with systemic immunotherapy (ipilimumab and/or PD1 inhibitor) within 4 weeks of surgery.

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)
Permuted block randomisation, stratified by tumour site (nodal disease ± skin, or skin metastases only), and previous systemic immunotherapy or not.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/11/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26555 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 26556 0
The Poche Centre, Melanoma Institute Australia - North Sydney
Recruitment postcode(s) [1] 42595 0
2050 - Camperdown
Recruitment postcode(s) [2] 42596 0
2060 - North Sydney

Funding & Sponsors
Funding source category [1] 316538 0
Other Collaborative groups
Name [1] 316538 0
Sydney Cancer Partners
Country [1] 316538 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Country
Australia
Secondary sponsor category [1] 318728 0
None
Name [1] 318728 0
Address [1] 318728 0
Country [1] 318728 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315331 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 315331 0
https://www.slhd.nsw.gov.au/rpa/research/
Ethics committee country [1] 315331 0
Australia
Date submitted for ethics approval [1] 315331 0
29/01/2024
Approval date [1] 315331 0
30/04/2024
Ethics approval number [1] 315331 0
X24-0018 & 2024/ETH00095

Summary
Brief summary
The aim of the study is to see whether taking a drug known as a COX-2 inhibitor (used for arthritis), and another known as a Beta blocker (used for heart rhythm management), for a number of days before and after surgery, has an impact on inflammation and stress hormones in patients with Stage III melanoma (such as melanoma in lymph nodes).

Who is it for?
You may be eligible for this study if you are an adult patient with known metastatic cutaneous melanoma in lymph nodes and/or in transit recurrences in skin, measuring at least 0.5cm in largest diameter, appropriate for surgical management and where surgery is expected to render the patient clinically disease free.

Study details
Participants will be randomly allocated to take a regimen of two drugs (propanolol and celecoxib) orally for a number of days before and after surgery, or to a standard care arm where participants will undergo surgery without an additional drug regimen. Participants will be asked to provide blood samples and complete questionnaires relating to their quality of life at baseline and up to 4 months after surgery.

It is hoped that findings from this study will inform future studies on the effect of perioperative propanolol and celecoxib on recurrence rates of melanoma in patients with Stage III disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134366 0
A/Prof Robyn Saw
Address 134366 0
Department of Melanoma and Surgical Oncology, Gloucester House 3, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050
Country 134366 0
Australia
Phone 134366 0
+61 2 9515 5072
Fax 134366 0
Email 134366 0
[email protected]
Contact person for public queries
Name 134367 0
Dr Katina Selvaraj
Address 134367 0
Department of Dermatology, Gloucester House 3, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050
Country 134367 0
Australia
Phone 134367 0
+61 2 9515 3629
Fax 134367 0
Email 134367 0
[email protected]
Contact person for scientific queries
Name 134368 0
Dr Katina Selvaraj
Address 134368 0
Department of Dermatology, Gloucester House 3, Royal Prince Alfred Hospital, Missenden Road, Camperdown NSW 2050
Country 134368 0
Australia
Phone 134368 0
+61 2 9515 3629
Fax 134368 0
Email 134368 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.