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

Sponsor
Onxeo (Industry)
Overall Status
Completed
CT.gov ID
NCT00548704
Collaborator
(none)
57
Enrollment
34
Locations
40
Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
57 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-cancer Agents
Study Start Date :
Apr 1, 2002
Actual Primary Completion Date :
Aug 1, 2005
Actual Study Completion Date :
Aug 1, 2005

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

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

    5. 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.

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

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

    8. 18 years of age or older

    9. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Aalborg Hospital South Aalborg Denmark 9100
    2 Aarhus County Hospital Aarhus Denmark 8000 C
    3 Aarhus Municipality Hospital Aarhus Denmark 8000 C
    4 Rigshospitalet, Haematology Department Copenhagen Denmark 2100
    5 Rigshospitalet, Oncology Department Copenhagen Denmark 2100
    6 Esbjerg District Hospital Esbjerg Denmark 6700
    7 Herlev County Hospital, Haematology Department Herlev Denmark 2730
    8 Herlev County Hospital, Oncology Department Herlev Denmark 2730
    9 Hilleroed Hospital Hilleroed Denmark 3400
    10 Naestved District Hospital Naestved Denmark 4700
    11 Odense University Hospital Odense Denmark 5000 C
    12 Roskilde County Hospital Roskilde Denmark 4000
    13 Soenderborg Hospital Soenderborg Denmark 6400
    14 Vejle Hospital Vejle Denmark 7100
    15 Viborg Hospital Viborg Denmark 8800
    16 Evangelisches Bethesda Krankenhaus Essen Borbak Statt Germany 45355
    17 Klinik für Gynäkologie und Geburtshilfe Frankfurt am Main Germany 60590
    18 Klinik und Poliklinik für Innere Medizin Hamburg Germany 20246
    19 Medizinische Hochschule Hannover Hannover Germany 30659
    20 Universitäts Frauenklinik Kiel Germany 24105
    21 Universitäts Medizinische Klinik Kiel Germany 24105
    22 Frauenklinik com Roten Kreuz Munich Germany 80637
    23 Universitäts Frauenklinik Rostock Germany 18057
    24 Klinik für Gynäkologie und Gynäkologische Onkologie Wiesbaden Germany 65199
    25 Ospedale G.B. Morgagni L. Pierantoni Forli Italy 47100
    26 Presidio Ospedaliero di Ravenna Ravenna Italy 48100
    27 Ospedale degli Infermi Rimini Italy 47037
    28 Ospedali Riuniti Trieste Italy 34100
    29 Netherland Cancer Institute Amsterdam Netherlands 1066 CX
    30 University Hospital Groningen Netherlands 9700 RB
    31 Willem Alexander Hospital Hertogenbosch Netherlands 5223 GV
    32 Centre of Oncology - Krakow Division Krakow Poland 31-115
    33 Maria Sklodowska-Curie Memorial Cancer Center Warsaw Poland 02-781
    34 Dolnoslaski Centrum Onkologii oddzial Chemoterapii Wroclaw Poland 53-413

    Sponsors and Collaborators

    • Onxeo

    Investigators

    • Principal Investigator: Henning T Mouridsen, MD, Dr. med., Rigshospitalet, The Finsen Centre 5074, Blegdamsvej 9, DK-2100 Copenhagen

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Onxeo
    ClinicalTrials.gov Identifier:
    NCT00548704
    Other Study ID Numbers:
    • TT02
    First Posted:
    Oct 24, 2007
    Last Update Posted:
    Oct 21, 2015
    Last Verified:
    Nov 1, 2013
    Keywords provided by Onxeo
    Extravasation
    Anthracyclines
    Additional relevant MeSH terms:
    Dexrazoxane
    Razoxane

    Study Results

    No Results Posted as of Oct 21, 2015