Perioperative Treatment with Tranexamic Acid in Melanoma (PRIME)

University of Aarhus

Status and phase: Enrolling; Phase 3

Conditions: Melanoma

Treatments: Drug: Tranexamic acid; Drug: Saline

Study type: Interventional

Funder types: Other

Identifiers

NCT05899465

PRIME

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,204 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,204 participants in 2 patient groups, including a placebo group

Tranexamic Acid

Experimental group

Description:

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.

Treatment:

Drug: Tranexamic acid

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Saline