Does peri-operative treatment with Tranexamic Acid reduce the early relapse rate for patients with melanoma; a randomised controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aarhus University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Neoplasms [C04]

Trial duration

25 Aug 2023 → ongoing

Decision date (initial)

2023-03-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Danish Cancer Society, ACROBATIC (Dansk Forskningscenter for Kræftkirurgi), NEYE fonden

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To test if perioperative treatment with TXA is superior to placebo and reduces the early relapse rates by >10%, for patients diagnosed with melanoma undergoing sentinel lymph node biopsy surgery.

Secondary objectives 5

1. Evaluate safety and tolerability: defined as mild (abdominal pain, diarrhoea, 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 between the two treatment groups.
4. From blood samples, at predefined timepoints, we monitor baseline and perioperative changes of factors associated with systemic inflammation, fibrinolysis, and metabolism, immune cell composition and activation status, and associate these factors with prognostic and treatment related outcomes.
5. From tissue samples of the primary melanoma biopsy, local wide excisions and corresponding metastases, we will conduct fluorescence multiplex stainings and spatial transcriptomic, and analyse markers of the plasminogen-plasmin pathway, inflammation, and metabolism, and evaluate their roles as prognostic and predictive biomarkers.

Conditions and MedDRA coding

Melanoma Surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients: Diagnosed with invasive cutaneous melanoma (pathological stage/tumor grade higher than 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 1

1. Patients: With prior history of invasive melanoma Thromboembolic events within the last 3 months Pregnancy * Active breast feeding Known allergy or hypersensitivity to TXA Known and treated epilepsia or previous seizures eGFR 0-50

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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. We will calculate relapse risk proportions for each treatment arm as a binary outcome.

Secondary endpoints 5

1. Adverse events, summarised according to grade: Mild: defined as the patient’s report of abdominal pain, diarrhoea or nausea. Severe: thromboembolic events, verified radiologically.
2. Postoperative complications, summarised according to the type and postoperative timepoint, is defined as binary outcomes as bleeding, seroma or infection
3. Melanoma specific survival: 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 (histopathological confirmed relapse or systemic metastases suspected on PET / CT / MR) or the date of completed 5 years follow-up.
4. Overall survival: 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 5 years follow-up.
5. Relapse free survival: defined as the period from the date of surgery (re-excision and sentinel node) to the date of histopathological confirmed relapse (local, regional or systemic), death from all causes or the data or completed 2 years follow-up.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aarhus University Hospital

Sponsor organisation

Aarhus University Hospital

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus University Hospital

Contact name

Marie Louise Bønnelykke-Behrndtz

Public contact point

Organisation

Aarhus University Hospital

Contact name

Marie Louise Bønnelykke-Behrndtz

Third parties 1

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

4 submissions — initial application plus substantial / non-substantial modifications