Perioperative Treatment with Tranexamic Acid in Melanoma; Prognostic and Treatment-related Impact of the Plasminogen-plasmin Pathway
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,204
- 试验地点
- 5
- 主要终点
- Difference in rate of relapse within two years when comparing treatment arms
研究概览
简要总结
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.
详细描述
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:
- Evaluate safety and tolerability: defined as mild (abdominal pain, diarrhea, or nausea) or severe (thromboembolic events) adverse effects.
- Evaluate postoperative complications: defined as bleeding, seroma formation, and infections within the first three postoperative months.
- Estimate melanoma-specific survival probabilities and compare the two treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Tranexamic Acid
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.
干预措施: Tranexamic acid (Drug)
Placebo
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.
干预措施: Saline (Drug)
结局指标
主要结局
Difference in rate of relapse within two years when comparing treatment arms
时间窗: 2 year follow-up
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.
次要结局
- Incidence of treatment-related adverse events(6 months follow-up)
- Relapse free survival(2 year follow-up)
- Overall survival(2 year follow-up)
- Assessment of incidens of postoperative complications(3 months follow-up)
- Melanoma-specific survival(2 year follow-up)