A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracyclines

Extravasation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00548704
• Other study ID #: TT02
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 23, 2007
• Last updated: October 20, 2015
• Start date: April 2002
• Est. completion date: August 2005

Study information

• Verified date: November 2013
• Source: Onxeo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics CommitteeDenmark: Danish Medicines AgencyNetherlands: Medical Ethics Review Committee (METC)Germany: Ethics CommissionItaly: Ethics CommitteePoland: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is

• To prevent progression of a lesion caused by anthracycline extravasation into necrosis, which would require surgical intervention

• To prevent development of deep tissue necrosis and destruction leading to impaired limb function and neurological deficit

• To prevent postponement of the scheduled cancer treatment due to the treatment of the extravasation

Description:

Accidental extravasation of anthracyclines, e.g. doxorubicin and its derivative epirubicin, may cause progressive tissue destruction including serious damage of the skin, the subcutaneous tissue, muscles, and nerves.

The patient may suffer from acute local symptoms such as pain and swelling, which may progress into blistering and necrosis. Subsequently dysesthesia, skin atrophy, disfigurement, and impaired limb function may be the consequence.

Surgical removal of all affected tissue is required and the debridement often necessitates split skin grafting. The patient is thus subjected to the distress of major surgery, which in turn leads to delay of further cytotoxic treatment.

Preclinical animal studies as well as a clinical multicenter phase II trial have demonstrated a highly significant efficacy of dexrazoxane in preventing tissue destruction caused by anthracyclines.

This confirmatory trial will determine the effect of Topotect® (dexrazoxane) as an acute antidote in patients with anthracycline extravasation.

Orphan drug status TopoTarget A/S was granted designation for Topotect® as an orphan medical product for the treatment of anthracycline extravasations by the European Commission in September 2001 and by the FDA in ???.

Purpose

Primary objectives:

• To prevent progression of the anthracycline extravasation lesion as tissue ulceration and necrosis requiring surgical intervention

Secondary objectives:

• To prevent development of deep tissue necrosis and destruction leading to late sequelae as impaired limb function and neurological deficit

• To prevent postponement of the scheduled cancer treatment due to the treatment of the extravasation

• To evaluate the tolerance to and/or toxicity of Topotect® used for this indication, according to the indicated schedule

Trial design This is an open-label, non-randomised phase II/III trial. Thirty -five evaluable patients with anthracycline extravasations will be treated.

Extravasation is determined by the presence of pain, and/or swelling, and/or redness at the site where anthracycline leakage is suspected to have occurred. The extravasations are subsequently confirmed in each patient by fluorescence microscopy of at least two punch biopsies at the time of the accident.

Success criteria The prevention of surgical intervention, necrosis and late sequelae evaluated 3 months after the extravasation.

Safety features

• Toxicity caused by Topotect® will be examined by haematology and blood chemistry, questions are asked on any discomfort. Scheduled clinical examinations are performed

• A systematic clinical evaluation of the marked area of skin covering the area of extravasation will be performed in order to evaluate the need for surgery

• Sequential colour photographs of the involved skin will be taken

Medical Treatment Patients are treated with intravenous infusion of Topotect® administered once daily on three consecutive days at the following doses: 1,000 mg/m2 + 1,000 mg/m2 + 500 mg/m2. The first dose is administered as soon as possible and within 6 hours of the extravasation and the next two doses at 24 and 48 hours after the first infusion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: August 2005
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. All cancer patients treated with anthracyclines

2. Informed consent must be obtained from the patient

3. Patients suspected to have been exposed to extravasation (leakage) of anthracycline, defined as:

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

2. The presence of at least one of the following symptoms: pain, swelling or redness at the site where the anthracycline leakage is suspected to have occurred.

4. Suspicion of anthracycline extravasation from a central venous access device

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

6. 18 years of age or older

7. Performance status (PS) < 2

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 (aspartate aminotransferase) or ALT (alanine aminotransferase), bilirubin, LDH (lactate dehydrogenase), alkaline phosphatase >3 x upper normal value

4. Neutrophils CTC (common toxicity criteria) = grade 2. (neutrophils 1.5 x 109/L, =1,500/mm3)

5. Platelets CTC = grade 2. (platelets =75.0 x 109/L, <75,000/mm3).

6. Topical use of DMSO (dimethylsulfoxide) at the area of the accident

7. Administration of dexrazoxane within the last 3 weeks

8. Pregnant or nursing women

9. Women of childbearing age and potential, who do not use an efficient contraceptive (e.g. the Pill or a diaphragm plus a spermicide) for at least 3 months prior to the start of trial medication

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

• Extravasation

Intervention

Drug:
• Dexrazoxane

Locations

Country	Name	City	State
Denmark	Aalborg Hospital South	Aalborg
Denmark	Aarhus County Hospital	Aarhus
Denmark	Aarhus Municipality Hospital	Aarhus
Denmark	Rigshospitalet, Haematology Department	Copenhagen
Denmark	Rigshospitalet, Oncology Department	Copenhagen
Denmark	Esbjerg District Hospital	Esbjerg
Denmark	Herlev County Hospital, Haematology Department	Herlev
Denmark	Herlev County Hospital, Oncology Department	Herlev
Denmark	Hilleroed Hospital	Hilleroed
Denmark	Naestved District Hospital	Naestved
Denmark	Odense University Hospital	Odense
Denmark	Roskilde County Hospital	Roskilde
Denmark	Soenderborg Hospital	Soenderborg
Denmark	Vejle Hospital	Vejle
Denmark	Viborg Hospital	Viborg
Germany	Evangelisches Bethesda Krankenhaus	Essen Borbak Statt
Germany	Klinik für Gynäkologie und Geburtshilfe	Frankfurt am Main
Germany	Klinik und Poliklinik für Innere Medizin	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitäts Frauenklinik	Kiel
Germany	Universitäts Medizinische Klinik	Kiel
Germany	Frauenklinik com Roten Kreuz	Munich
Germany	Universitäts Frauenklinik	Rostock
Germany	Klinik für Gynäkologie und Gynäkologische Onkologie	Wiesbaden
Italy	Ospedale G.B. Morgagni L. Pierantoni	Forli
Italy	Presidio Ospedaliero di Ravenna	Ravenna
Italy	Ospedale degli Infermi	Rimini
Italy	Ospedali Riuniti	Trieste
Netherlands	Netherland Cancer Institute	Amsterdam
Netherlands	University Hospital	Groningen
Netherlands	Willem Alexander Hospital	Hertogenbosch
Poland	Centre of Oncology - Krakow Division	Krakow
Poland	Maria Sklodowska-Curie Memorial Cancer Center	Warsaw
Poland	Dolnoslaski Centrum Onkologii oddzial Chemoterapii	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
Onxeo

Countries where clinical trial is conducted

Denmark,  Germany,  Italy,  Netherlands,  Poland, 

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