Antineoplastic Agents

Cardiotonic Agents

All Drugs and Chemicals

Dexrazoxane

Razoxane

Enzyme Inhibitors

Protective Agents

Antimitotic Agents

Henning T Mouridsen, MD, Dr. med.

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

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.

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

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

Valerio Therapeutics

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

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.

Efficacy of TopotectTM (Dexrazoxane) for Accidental Extravasation of Anthracyclines

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

Dexrazoxane should be given once daily for 3 consecutive days. The dose is:

Day 1: 1000 mg/m2, Day 2: 1000 mg/m2, Day 3: 500 mg/m2 (body surface area)

Tatsuro Takei

The purpose of this study is to evaluate the efficacy and safety of KDX-0811(Dexrazoxane) in the treatment of accidental extravasation of anthracycline anti-cancer agents.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracyclines	NCT00548704	Extravasation	Dexrazoxane	18 Years -	Valerio Therapeutics
A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracyclines	NCT00548704	Extravasation	Dexrazoxane	18 Years -	Valerio Therapeutics
Efficacy of TopotectTM (Dexrazoxane) for Accidental Extravasation of Anthracyclines	NCT00548561	Anthracycline E...	Dexrazoxane	18 Years -	Valerio Therapeutics
A Phase I/II Study of KDX-0811(Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-cancer Agents	NCT01596088	Extravasations ...	Dexrazoxane	20 Years -	Kissei Pharmaceutical Co., Ltd.

Spots Global Cancer Trial Database for extravasation