None listed
Conditions
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.
Interventions
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 tabl
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.
Sponsors
Sydney Local Health District
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed