ExtravasationPhase 2/3NCT00548704
A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracyclines
A Phase 2/3 study testing Dexrazoxane in people with Extravasation, run by Valerio Therapeutics at 34 sites in 5 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extravasation
- What is being tested?
- Dexrazoxane
- How many people
- 57 participants
- Where
- 34 sitesin 5 countries
- Study dates
- Apr 2002to Aug 2005
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All cancer patients treated with anthracyclines
- Informed consent must be obtained from the patient
- Patients suspected to have been exposed to extravasation (leakage) of anthracycline, 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 symptoms: pain, swelling or redness at the site where the anthracycline leakage is suspected to have occurred.
- Suspicion of anthracycline extravasation from a central venous access device
Show all 9Show fewer
- The Topotect® infusion must be started < 6 hours after the accident
- 18 years of age or older
- Performance status (PS) < 2
Who cannot join
- 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 (aspartate aminotransferase) or ALT (alanine aminotransferase), bilirubin, LDH (lactate dehydrogenase), alkaline phosphatase >3 x upper normal value
- Neutrophils CTC (common toxicity criteria) ≥ grade 2. (neutrophils 1.5 x 109/L, ≥1,500/mm3)
- Platelets CTC ≥ grade 2. (platelets ≥75.0 x 109/L, <75,000/mm3).
- Topical use of DMSO (dimethylsulfoxide) at the area of the accident
Show all 9Show fewer
- Administration of dexrazoxane within the last 3 weeks
- Pregnant or nursing women
- 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
Trial locations and contacts
34 sites in 5 countries.
34 sites in 5 countries
Denmark15 sites
Aalborg Hospital South
Aalborg, 9100
Aarhus County Hospital
Aarhus, 8000 C
Aarhus Municipality Hospital
Aarhus, 8000 C
Rigshospitalet, Haematology Department
Copenhagen, 2100
Rigshospitalet, Oncology Department
Copenhagen, 2100
Esbjerg District Hospital
Esbjerg, 6700
Herlev County Hospital, Haematology Department
Herlev, 2730
Herlev County Hospital, Oncology Department
Herlev, 2730
Hilleroed Hospital
Hilleroed, 3400
Naestved District Hospital
Næstved, 4700
Odense University Hospital
Odense, 5000 C
Roskilde County Hospital
Roskilde, 4000
Soenderborg Hospital
Sønderborg, 6400
Vejle Hospital
Vejle, 7100
Viborg Hospital
Viborg, 8800
Germany9 sites
Evangelisches Bethesda Krankenhaus
Essen Borbak Statt, 45355
Klinik für Gynäkologie und Geburtshilfe
Frankfurt am Main, 60590
Klinik und Poliklinik für Innere Medizin
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, 30659
Universitäts Frauenklinik
Kiel, 24105
Universitäts Medizinische Klinik
Kiel, 24105
Frauenklinik com Roten Kreuz
Munich, 80637
Universitäts Frauenklinik
Rostock, 18057
Klinik für Gynäkologie und Gynäkologische Onkologie
Wiesbaden, 65199
Italy4 sites
Ospedale G.B. Morgagni L. Pierantoni
Forlì, 47100
Presidio Ospedaliero di Ravenna
Ravenna, 48100
Ospedale degli Infermi
Rimini, 47037
Ospedali Riuniti
Trieste, 34100
Netherlands3 sites
Willem Alexander Hospital
's-Hertogenbosch, 5223 GV
Netherland Cancer Institute
Amsterdam, 1066 CX
University Hospital
Groningen, 9700 RB
Poland3 sites
Centre of Oncology - Krakow Division
Krakow, 31-115
Maria Sklodowska-Curie Memorial Cancer Center
Warsaw, 02-781
Dolnoslaski Centrum Onkologii oddzial Chemoterapii
Wroclaw, 53-413
About this study
Official title: A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-cancer Agents
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
Read the 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.
- Conditions
- Extravasation
- Being tested
- Dexrazoxane
- Keywords
- Extravasation, Anthracyclines
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexrazoxaneDrug
Also called Totect
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2007 (estimated)
- Study startApr 2002
- Primary completionAug 2005
- Study completionAug 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ExtravasationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Valerio Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Henning T Mouridsen, MD, Dr. med., Principal investigator, Rigshospitalet, The Finsen Centre 5074, Blegdamsvej 9, DK-2100 Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00548704
- Sponsor's protocol ID
- TT02
- Status last verified
- Nov 2013
- First submitted
- 23 Oct 2007
- Last updated
- 21 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 17185744
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial on Topotect® (Dexrazoxane) in the Treatment of Accidental Extravasation of Anthracycline Anti-cancer Agents
- ClinicalTrials.gov ID
- NCT00548704
- Acronym / sponsor ID
- TT02
- Conditions
- Extravasation
- Keywords
- Extravasation, Anthracyclines
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Valerio TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Apr 2002
- Primary completion
- Aug 2005 (actual)
- Study completion
- Aug 2005 (actual)
- First posted
- 24 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- All cancer patients treated with anthracyclines
- Informed consent must be obtained from the patient
- Patients suspected to have been exposed to extravasation (leakage) of anthracycline, defined as:
- Suspicion of anthracycline extravasation from a central venous access device
- The Topotect® infusion must be started < 6 hours after the accident
Key exclusion criteria (9 listed)
- 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 (aspartate aminotransferase) or ALT (alanine aminotransferase), bilirubin, LDH (lactate dehydrogenase), alkaline phosphatase >3 x upper normal value
- Neutrophils CTC (common toxicity criteria) ≥ grade 2. (neutrophils 1.5 x 109/L, ≥1,500/mm3)
- Platelets CTC ≥ grade 2. (platelets ≥75.0 x 109/L, <75,000/mm3).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexrazoxaneAlso: Totect | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2015.
- Results publication: PubMed 17185744Mouridsen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henning T Mouridsen, MD, Dr. med. principal investigator
Rigshospitalet, The Finsen Centre 5074, Blegdamsvej 9, DK-2100 Copenhagen
34 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dexrazoxane in people with Extravasation, run by Valerio Therapeutics at 34 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in Denmark, Germany, Italy, Netherlands, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00548704, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2015.