Perioperative Treatment With Tranexamic Acid in Melanoma

Официальное название

Perioperative Treatment With Tranexamic Acid in Melanoma; Prognostic and Treatment-related Impact of the Plasminogen-plasmin Pathway

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Tranexamic acid
  A single preoperative intravenous dose and per os treatment postoperatively day 1 through 4
• Препарат Saline
  A single preoperative intravenous dose and per os treatment postoperatively day 1 through 4

Первичные конечные точки

• Difference in rate of relapse within two years when comparing treatment arms [Срок оценки: 2 year follow-up]

Вторичные конечные точки (5)

• Incidence of treatment-related adverse events [Срок оценки: 6 months follow-up]
• Assessment of incidens of postoperative complications [Срок оценки: 3 months follow-up]
• Melanoma-specific survival [Срок оценки: 2 year follow-up]
• Overall survival [Срок оценки: 2 year follow-up]
• Relapse free survival [Срок оценки: 2 year follow-up]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Дания · 5 центров

• Aarhus University Hospital. Dept. of Plastic- and Breast Surgery — Aarhus
• Aalborg University Hospital. Dept. of Plastic- and Breast Surgery. — Aalborg
• Copgenhagen University Hospital, Rigshospitalet. Dept. of Plastic Surgery and Burns Treatm — Copenhagen
• Copenhagen University Hospital, Herlev. Dept. of Plastic Surgery — Herlev
• Sygehus Lillebælt, Vejle Hospital. Dept. of Plastic Surgery — Vejle

Публикации

• 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

Идентификаторы

NCT: NCT05899465 · PRIME

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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