Efficacy of TopotectTM (Dexrazoxane) for Accidental Extravasation of Anthracyclines

Anthracycline Extravasation Clinical Trial

Official title:

A Clinical Trial on TopotectTM (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-cancer Agents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00548561
• Other study ID #: TT01
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 23, 2007
• Last updated: October 20, 2015
• Start date: June 2001
• Est. completion date: July 2003

Study information

• Verified date: November 2013
• Source: Onxeo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics CommitteeDenmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to avoid surgical intervention following extravasation of anthracycline chemotherapy out of a vessel into the surrounding tissues.

Description:

Accidental extravasation of anthracyclines including doxorubicin and its derivative epirubicin, may cause severe, progressive tissue necrosis requiring the surgical removal of any damaged tissue. Thus, the patient is subjected to major surgery causing substantial delay of the treatment of the primary cancer disease.

Tissue infiltration by anthracyclines may be detected by fluorescence microscopy. This test is performed at most hospitals in Denmark.

In a large preclinical trial, as well as 4 clinical cases, dexrazoxane has proven to prevent these severe tissue necroses. This trial will determine the effect of dexrazoxane as an acute treatment (acute antidote) in patients with anthracycline extravasation verified by fluorescence biopsy.

Purpose

Primary:

• To avoid surgical intervention following the accidental extravasation of anthracycline drug, and thus preventing the patient from sequelae.

Secondary:

• To avoid deleterious postponement of the cancer treatment itself.

• To evaluate and describe subjective and objective symptoms in the damaged area following treatment with TopotectTM.

• To evaluate tolerability/toxicity of TopotectTM used for this indication, according to the indicated schedule.

Trial Population 25 patients with accidental anthracycline extravasation confirmed by fluorescence microscopy

Trial Design Open-label clinical trial. Twenty-five consecutive patients with an acute (<6 hours) history of anthracycline extravasation confirmed by fluorescence microscopy (who in general practice are candidates for acute plastic surgical intervention) will be included.

Effect Variables Response rates, presence of late sequelae, time to progression, and clinical consequence of progression.

Safety Features

• Any toxicity caused by TopotectTM will be studied by blood tests, systematic questioning regarding subjective discomfort, as well as by objective clinical examination.

• A systematic clinical evaluation of the marked area of skin covering the area of extravasation will be performed to assure prompt treatment should any deterioration occur.

• Sequential colour photographs of the involved skin area will be taken.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: July 2003
• Est. primary completion date: July 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Cancer patients treated with anthracycline

2. Informed consent obtained from the patient.

3. Suspicion of anthracycline extravasation is defined as:

A primary assessment by the physician on duty, which would activate the standard departmental procedure for treatment of anthracycline extravasation.

The presence of at least one of the following:

• pain

• swelling

• redness

4. The Topotect infusion must be started <6 hours after the accident.

5. The patient must be at least 18 years of age.

6. Performance status (PS) =2.

7. Suspicion of anthracycline extravasation from a central venous access device. -

Exclusion Criteria:

1. Known allergy towards dexrazoxane.

2. Reasonable suspicion of extravasation by other compounds than anthracyclines through the same intravenous access, e.g. vincristine, mitomycin, and vinorelbine, all of which may cause ulceration.

3. AST, ALT, bilirubin, LDH, serum alkaline phosphatase >3 x upper normal value

4. Neutropenia and thrombocytopenia = CTC grade 2

5. Pregnant or nursing women

6. Women of childbearing age and potential, where the patient does not agree to use an efficient contraceptive (e.g. birth control pill or an intra-uterine device for 3 months previous to start of the trial medication or diaphragm plus a spermicide).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anthracycline Extravasation

Intervention

Drug:
• Dexrazoxane

Locations

Country	Name	City	State
Denmark	Aalborg Hospital South	Aalborg
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev County Hospital	Herlev
Denmark	Herlev Hospital Hematological Department	Herlev
Denmark	Herning District Hospital	Herning
Denmark	Hilleroed Hospital	Hilleroed
Denmark	Odense University Hospital	Odense
Denmark	Roskilde County Hospital	Roskilde
Denmark	Viborg Hospital	Viborg

Sponsors (1)

Lead Sponsor	Collaborator
Onxeo

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Mouridsen HT, Langer SW, Buter J, Eidtmann H, Rosti G, de Wit M, Knoblauch P, Rasmussen A, Dahlstrøm K, Jensen PB, Giaccone G. Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies. A — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of surgical resection necessity by progressing necrosis