Perioperative Treatment With Tranexamic Acid in Melanoma

NCT05899465 | Recruiting Phase 3 DMC

• 1 other identifier: PRIME
• Study Type: interventional
• Target: 1,204
• Locations: 1 country
• Sites: 5

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.

Conditions

Melanoma

Keywords

Melanoma; Tranexamic acid; Relapse; Cancer; Drug Repositioning; Surgery

Outcome Measures

Primary Outcomes (1)

• Difference in rate of relapse within two years when comparing treatment arms

  Histopathological confirmed relapse, defined as either local, regional (in transit or lymph node) or systemic relapses. Systemic metastases suspected on PET / CT/ MR will be used if a biopsy is not possible. Based on the primary endpoint, we will calculate the relapse risk proportions for each treatment arm as a binary outcome. The date of relapse or completed follow-up is noted and the relapse-free period is defined as the date of wide local excision and sentinel lymph node biopsy until the date of either the first confirmed relapse or the date of completed two-year follow-up without relapse.

  2 year follow-up

Secondary Outcomes (5)

• Incidence of treatment-related adverse events

  6 months follow-up

• Assessment of incidens of postoperative complications

  3 months follow-up

• Melanoma-specific survival

  2 year follow-up

• Overall survival

  2 year follow-up

• Relapse free survival

  2 year follow-up

Study Arms (2)

Tranexamic Acid

EXPERIMENTAL

A single dose of TXA (15 mg/kg) administered intravenously 30 min (+/-15 min) before skin incision and subsequently, TXA (1000 mg) administered orally 4 and 8 hours post-surgery and TXA (1000 mg) 3 times daily through postoperative day 4.

Drug: Tranexamic acid

Placebo

PLACEBO COMPARATOR

A single dose of saline matching the volume of the experimental arm treatment regiment (Saline) administered intravenously 30 min (+/-15 min) before skin incision and subsequently, placebo tablets (2 tabs.) administered orally 4 and 8 hours post-surgery and (2 tabs) 3 times daily through postoperative day 4.

Drug: Saline

Interventions

Tranexamic acid DRUG

A single preoperative intravenous dose and per os treatment postoperatively day 1 through 4

Tranexamic Acid

Saline DRUG

A single preoperative intravenous dose and per os treatment postoperatively day 1 through 4

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Central Denmark Region: collaborator

Study Sites (5)

Aarhus University Hospital. Dept. of Plastic- and Breast Surgery

Aarhus, Central Jutland, Denmark

RECRUITING

Aalborg University Hospital. Dept. of Plastic- and Breast Surgery.

Aalborg, North Denmark, Denmark

RECRUITING

Copgenhagen University Hospital, Rigshospitalet. Dept. of Plastic Surgery and Burns Treatment

Copenhagen, Denmark

RECRUITING

Copenhagen University Hospital, Herlev. Dept. of Plastic Surgery

Herlev, Denmark

ACTIVE NOT RECRUITING

Sygehus Lillebælt, Vejle Hospital. Dept. of Plastic Surgery

Vejle, Denmark

ACTIVE NOT RECRUITING

Related Publications (1)

• Kristjansen KA, Engel Krag A, Schmidt H, Holmich LR, Bonnelykke-Behrndtz ML. Perioperative treatment with tranexamic acid in melanoma (PRIME): protocol for a Danish multicentre randomised controlled trial investigating the prognostic and treatment-related impact of the plasminogen-plasmin pathway. BMJ Open. 2024 Feb 2;14(2):e077012. doi: 10.1136/bmjopen-2023-077012.

  PMID: 38309757 DERIVED

MeSH Terms

Conditions

Melanoma; Recurrence; Neoplasms

Interventions

Tranexamic Acid; Sodium Chloride

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Marie Louise Bønnelykke-Behrndtz, MD, PhD

CONTACT

+45 78 45 00 00; marboe@rm.dk

Karoline Kristjansen, MD

CONTACT

karoline_kristjansen@clin.au.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, investigators/outcome assessors are all blinded to the intervention. Selected trained personnel who does not treat or assess the participants will be unblinded to prepare the intervention for administration and deliver the intervention to blinded personnel for administration.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel, two-arm, randomized, blinded Danish multi-center trial

Study Record Dates

• First Submitted: April 4, 2023
• First Posted: June 12, 2023
• Study Start: August 25, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

DK (5)