Clinical trial NCT05899465: Perioperative Treatment With Tranexamic Acid in Melanoma
Official title: Perioperative Treatment With Tranexamic Acid in Melanoma; Prognostic and Treatment-related Impact of the Plasminogen-plasmin Pathway
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Melanoma
Keywords: Melanoma
Tranexamic acid
Relapse
Cancer
Drug Repositioning
Surgery
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Central Denmark Region
First posted: 2023-06-12
Enrollment: 1204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel, two-arm, randomized, blinded Danish multi-center trial
Primary purpose: PREVENTION

Brief summary: Surgery is a key element in the treatment of melanoma, and naturally linked with an inflammatory response and recruitment of innate immune cells. Although surgery has a favorable intent, surgery-induced inflammation, neutrophils in particular, may accelerate growth of local and systemic micrometastases. Thus, improving cancer surgery and modulating the wound microenvironment in ways that benefit the patients is crucial.

Repurposing already approved drugs in a cancer setting has gained increasing interest in recent years. Interestingly, tranexamic acid was recently suggested as an anti-cancer drug, capable of reducing tumor growth in experimental animal models and reducing the viability of different melanoma cell lines.

As a novel approach, sponsor and investigators will conduct a Randomised Clinical Trial, using perioperative treatment with Tranexamic Acid, aiming to prevent the early relapses for patients with melanoma.

Detailed description: The objective of the proposed clinical trial is to test if perioperative treatment with tranexamic acid (TXA) reduces the early relapses and postoperative complications for patients with melanoma and evaluate perioperative inflammation and the prognostic- and treatment-related impact of the plasminogen-plasmin pathway from human blood- and tissue samples.

Primary aim:

To test if perioperative treatment with TXA is superior to placebo and reduces the early relapse rates, from 37% to 26%, for patients diagnosed with melanoma undergoing sentinel lymph node biopsy surgery.

Secondary aims:

1. Evaluate safety and tolerability: defined as mild (abdominal pain, diarrhea, or nausea) or severe (thromboembolic events) adverse effects.
2. Evaluate postoperative complications: defined as bleeding, seroma formation, and infections within the first three postoperative months.
3. Estimate melanoma-specific survival probabilities and compare the two treatment groups.

Explorative:

From blood- and tissue samples, baseline and perioperative changes of factors associated with inflammation, fibrinolysis, metabolism, immune cell composition, and activation status will be monitored and factors will be associated with prognostic and treatment-related outcomes.

Eligibility criteria: Inclusion Criteria:

Patients

* Diagnosed with invasive cutaneous melanoma (pathological stage/tumor grade ≥T2b), defined as either: Breslow thickness \>1.0-2.0 mm with presence of ulceration or Breslow thickness \>2.0 mm regardless of ulceration status.
* Eligible for surgery (wide local excision and sentinel lymph node biopsy).
* \>/=18 years of age and \</=80 years of age
* Signed Informed Consent Form

Exclusion Criteria:

Patients

* With a prior history of invasive melanoma
* Thromboembolic events within the last 3 months
* Pregnancy
* Active breastfeeding
* Known allergy or hypersensitivity to TXA
* Known and treated epilepsia or previous seizures
* eGFR 0-50
* Current use of tranexamic acid

Primary outcomes:
measure: Difference in rate of relapse within two years when comparing treatment arms
timeFrame: 2 year follow-up
Secondary outcomes:
measure: Incidence of treatment-related adverse events
timeFrame: 6 months follow-up
measure: Assessment of incidens of postoperative complications
timeFrame: 3 months follow-up
measure: Melanoma-specific survival
timeFrame: 2 year follow-up
measure: Overall survival
timeFrame: 2 year follow-up
measure: Relapse free survival
timeFrame: 2 year follow-up
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital. Dept. of Plastic- and Breast Surgery
state: Central Denmark Region
city: Aalborg
country: Denmark
facility: Aalborg University Hospital. Dept. of Plastic- and Breast Surgery.
state: North Denmark Region
city: Copenhagen
country: Denmark
facility: Copgenhagen University Hospital, Rigshospitalet. Dept. of Plastic Surgery and Burns Treatment
city: Herlev
country: Denmark
facility: Copenhagen University Hospital, Herlev. Dept. of Plastic Surgery
city: Vejle
country: Denmark
facility: Sygehus Lillebælt, Vejle Hospital. Dept. of Plastic Surgery
Study officials:
References: