Clinical trial NCT00548561: Efficacy of TopotectTM (Dexrazoxane) for Accidental Extravasation of Anthracyclines
Official title: A Clinical Trial on TopotectTM (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-cancer Agents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Anthracycline Extravasation
Keywords: extravasation
anthracyclines
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-10-24
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 criteria: 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).

Primary outcomes:
measure: The rate of surgical resection necessity by progressing necrosis
Secondary outcomes:
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg Hospital South
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev County Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital Hematological Department
city: Herning
country: Denmark
facility: Herning District Hospital
city: Hilleroed
country: Denmark
facility: Hilleroed Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde County Hospital
city: Viborg
country: Denmark
facility: Viborg Hospital
Study officials:
affiliation: Rigshospitalet, The Finsen Centre 5074, Blegdamsvej 9, DK-2100 Copenhagen
name: Henning T Mouridsen, MD, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1093/annonc/mdl413. Epub 2006 Dec 21.