Efficacy of TopotectTM (Dexrazoxane) for Accidental Extravasation of Anthracyclines - Full Text View

Sponsored by:	TopoTarget A/S
Information provided by:	TopoTarget A/S
ClinicalTrials.gov Identifier:	NCT00548561

Purpose

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

Condition	Intervention	Phase
Anthracycline Extravasation	Drug: Dexrazoxane	Phase II Phase III

Drug Information available for: Dexrazoxane Dexrazoxane hydrochloride ICRF 159 Razoxane

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Clinical Trial on TopotectTM (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-Cancer Agents

Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:

The rate of surgical resection necessity by progressing necrosis

Estimated Enrollment:	25
Study Start Date:	July 2001
Estimated Study Completion Date:	July 2003

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Cancer patients treated with anthracycline
Informed consent obtained from the patient.
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
The Topotect infusion must be started <6 hours after the accident.
The patient must be at least 18 years of age.
Performance status (PS) ≤2.
Suspicion of anthracycline extravasation from a central venous access device. -

Exclusion Criteria:

Known allergy towards dexrazoxane.
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.
AST, ALT, bilirubin, LDH, serum alkaline phosphatase >3 x upper normal value
Neutropenia and thrombocytopenia ≥ CTC grade 2
Pregnant or nursing women
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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00548561

Locations

Denmark
Rigshospitalet
Copenhagen, Denmark, 2100
Herlev County Hospital
Herlev, Denmark, 2730
Naestved District Hospital
Naestved, Denmark, 4700
Hilleroed Hospital
Hilleroed, Denmark, 3400
Roskilde County Hospital
Roskilde, Denmark, 4000
Odense University Hospital
Odense, Denmark, 5000 C
Vejle Hospital
Vejle, Denmark, 7100
Herning District Hospital
Herning, Denmark, 7400
Aarhus County hospital
Aarhus, Denmark, 8000 C
Aalborg Hospital South
Aalborg, Denmark, 9100
Viborg Hospital
Viborg, Denmark, 8800
Soenderborg Hospital
Soenderborg, Denmark, 6400
Esbjerg District Hospital
Esbjerg, Denmark, 6700
Aarhus Municipality Hospital
Aarhus, Denmark, 8000 C

Sponsors and Collaborators

TopoTarget A/S

Investigators

Principal Investigator:

Henning T Mouridsen, MD, Dr. med.

Rigshospitalet, The Finsen Centre 5074, Blegdamsvej 9, DK-2100 Copenhagen

More Information

Publications of Results:

Mouridsen HT, Langer SW, Buter J, Eidtmann H, Rosti G, de Wit M, Knoblauch P, Rasmussen A, Dahlstrom K, Jensen PB, Giaccone G. Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies. Ann Oncol. 2007 Mar;18(3):546-50. Epub 2006 Dec 21.

Study ID Numbers:	TT01
Study First Received:	October 23, 2007
Last Updated:	October 23, 2007
ClinicalTrials.gov Identifier:	NCT00548561
Health Authority:	Denmark: Ethics Committee; Denmark: Danish Medicines Agency

Keywords provided by TopoTarget A/S:

extravasation
anthracyclines

Study placed in the following topic categories:

Razoxane

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Chelating Agents
Cardiovascular Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009