Perioperative Treatment With Tranexamic Acid in Melanoma

Melanoma Clinical Trial

— PRIME  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05899465
• Other study ID #: PRIME
• Status: Recruiting
• Phase: Phase 3
• Start date: August 25, 2023
• Est. completion date: September 1, 2028

Study information

• Verified date: August 2023
• Source: University of Aarhus
• Contact: Marie Louise Bønnelykke-Behrndtz, MD, PhD
• Phone: +45 78 45 00 00
• Email: marboe[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1204
• Est. completion date: September 1, 2028
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

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

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg	North Denmark Region
Denmark	Aarhus University Hospital	Aarhus	Central Denmark Region

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Central Denmark Region

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Incidence of treatment-related adverse events	Adverse events summarised according to grade: Mild: defined as the patient's report of abdominal pain, diarrhea, or nausea. Severe: thromboembolic events, verified radiologically.	6 months follow-up
Secondary	Assessment of incidens of postoperative complications	Postoperative complications, summarised according to the type and postoperative timepoint, is defined as binary outcomes: Bleeding: defined as a drained or surgically removed hematoma or suggillation of blood to the skin around the operated area, occurring within the first 10 days post-surgery.; Seroma: drained seroma, during the period from end of surgery through 3 months post-surgery.; Infection: local wound infection, treated with antibiotics or surgical intervention, during the period from end of surgery through 3 months post-surgery.	3 months follow-up
Secondary	Melanoma-specific survival	Time to event estimates: Defined as the period from the date of surgery (wide local excision and sentinel lymph node biopsy) to the date of death from suspected systemic melanoma (histopathologically confirmed relapse or systemic metastases suspected on PET / CT / MR) or the date of completed 2 years follow-up.	2 year follow-up
Secondary	Overall survival	Time to event estimates: Defined as the period from the date of surgery (re-excision and sentinel node) to the date of death from all causes or the date of finalised 2 years follow-up.	2 year follow-up
Secondary	Relapse free survival	Time to event estimates: Defined as the period from the date of surgery (re-excision and sentinel node) to the date of histopathologically confirmed relapse (local, regional or systemic), death from all causes or the data or completed 2 years follow-up.	2 year follow-up