KeloidsPhase 2NCT01425216
Sorafenib for Patients With Extensive Keloids
A Phase 2 study testing Sorafenib in people with Keloids, run by Tirgan, Michael H., M.D. at 1 site in United States.
Trial summary
Treatment of keloid disorder is an area of unmet medical need. Current treatments for keloid partially address small and localized keloids, yet there are no wholly satisfactory or effective treatments for patients with extensive keloids. Such patients may benefit from effective systemic treatments. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Keloids
- What is being tested?
- Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Mar 2013
- Phase
- Phase 2
- 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 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical Diagnosis of a keloid.
- Presence of extensive keloid disease as defined in section 1.3
- Age 18 to 50
- A signed informed consent document (ICD)
- Able and willing to receive sorafenib
- Patients must have normal end organ and marrow function
- Women of child-bearing potential must have a negative pregnancy test during screening. The effects of sorafenib on the developing human fetus are unknown. For this reason, women of child-bearing potential, and men, must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and three months beyond the last dose of sorafenib. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- -
Who cannot join
- Diastolic Blood pressure of 90 mm Hg or above
- History of any degree of hypertension, even medically controlled hypertension
- History of any form of cardiovascular disease or stroke
- History of any form of thromboembolic event
- History of renal dysfunction or proteinuria,
- History of any form of liver dysfunction
Show all 17Show fewer
- History of recent (past 12 month) or planned (next 9 months) major surgery,
- Men and women who plan to have children within 3 months of their last treatment
- Psychological Illness that may result in non compliance with treatment
- Patients receiving any other investigational agents.
- Patients with a history of serious allergic reactions to eggs (sorafenib is formulated using egg phospholipids).
- HIV-positive patients receiving combination anti-retroviral therapy are excluded because of possible pharmacokinetic interactions with the investigational agent.
- Patients who cannot swallow pills for whatever reason will be excluded.
- Patients having any history or current evidence of a bleeding diathesis.
- Patients who are taking, or have taken anticoagulants in past 12 months for any reason.
- Pregnancy and Breast Feeding Pregnant women are excluded from this study because sorafenib has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with sorafenib, breastfeeding is not allowed during the course of the study.
- Female patients will be advised not to get pregnant during the first 3 months from last administered dose of sorafenib. Men will be advised to continue using barrier method contraception and not father a child during the first 3 months from last administered dose of sorafenib
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Sorafenib in Patients With Extensive Keloids
Treatment of keloid disorder is an area of unmet medical need. Current treatments for keloid partially address small and localized keloids, yet there are no wholly satisfactory or effective treatments for patients with extensive keloids. Such patients may benefit from effective systemic treatments.
Sorafenib has the potential to regulate the three known dysregulated biological pathways in keloid tissue.
Read the detailed description
Dysregulation of several intracellular pathways have been reported by various investigators.
[A] Dysregulated apoptosis pathway: p53 mutations have been found in both hypertrophic scar and keloids fibroblasts from cultured cells to various extents. p53 plays a central role in the DNA damage response by inducing cell cycle arrest and/or apoptotic cell death. Time course experiments making cell cultures at different times to investigate the phenomenon of apoptosis and its involvement in the process of pathological scarring in both hypertrophic scars and keloid indicate to dysregulation of apoptotic pathways in Keloid tissue.
[B]Dysregulated TGF- β signaling: Transforming growth factor- β1 (TGF- β1) is well known as the crucial fibrogenic cytokine promoting ECM production and tissue fibrosis in keloid forming [9]. TGF- β1 is an essential profibrotic cytokine for collagen synthesis, and it is well known to increase mRNA expression of procollagen I. Administration of TGF- β1 resulted in a dramatic increase in intracellular collagen I levels in keloid fibroblasts. Due to the close relationship between TGF- β signaling and the production of collagen, blocking TGF- β signaling has the potential of repressing fibroblast proliferation and collagen synthesis, thereby preventing the formation of keloids.
[C]Dysregulated VEGF signaling pathway: VEGF (Vascular endothelial growth factor), one of the most widely studied secreted factors involved in angiogenesis, has been implicated as crucial to normal and pathological wound healing [18]. Gira et al. [19] indicated that VEGF production is abundant in the underlying dermis of keloids. In vitro studies have indicated that VEGF is expressed at higher levels in keloid-derived Fibroblasts than in normal skin Fibroblasts.
Sorafenib is an orally active multikinase inhibitor and has been reported to be an effective inhibitor of apoptosis, TGF-β signaling and VEGF pathway signaling, making it an ideal drug to test in the setting of extensive keloid disorder.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called Nexavar (sorafenib)
Treatment will be administered on an outpatient basis. All patients will keep a drug diary in order to record compliance with their drug regime. Sorafenib will be taken orally. Maximum length of treatment is 6 months. Starting dose of sorafenib is 200 mg three times per week for one month. In absence of Grade 2 toxicity, the dose will be increased on a monthly basis and will stop at 400 mg twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib arm | Experimental | All patients will be treated with sorafenib. Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (RR) of extensive keloids to sorafenib. RR is the sum of Complete Remission (CR) and Partial Remission (PR) at 12 month after last dose of sorafenib.
The primary objective of this trial is to demonstrate the efficacy of sorafenib in patients with extensive keloids.
Measured: 12 months
Secondary outcomes (1)
The secondary endpoint of this trial is to demonstrate the rate of AE and SAE following exposure to sorafenib measured while on treatment as well as at 1 year after the last dose of sorafenib.
The secondary objective of this trial is to demonstrate safety of sorafenib in this setting. Patients will be followed for one year after their last dose of sorafenib to assess safety of the treatment.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startMar 2013
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: IND application was not approved by the US FDA - Project was never started
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KeloidsStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tirgan, Michael H., M.D.
- Responsible party
- Sponsor
- Investigators
- Michael H Tirgan, MD, Principal investigator, St. Luke's Roosevelt Hospital Center, New York City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01425216
- Sponsor's protocol ID
- Tirgan 11-05
- Status last verified
- Oct 2016
- First submitted
- 19 Aug 2011
- Last updated
- 18 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Sorafenib in Patients With Extensive Keloids
- ClinicalTrials.gov ID
- NCT01425216
- Acronym / sponsor ID
- Tirgan 11-05
- Conditions
- Keloids
- Keywords
- Keloid, Patient who have extensive or massive keloids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: IND application was not approved by the US FDA - Project was never started
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Tirgan, Michael H., M.D.
- Study start
- Mar 2013
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 29 Aug 2011 (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.
Treatment of keloid disorder is an area of unmet medical need. Current treatments for keloid partially address small and localized keloids, yet there are no wholly satisfactory or effective treatments for patients with extensive keloids. Such patients may benefit from effective systemic treatments.
Sorafenib has the potential to regulate the three known dysregulated biological pathways in keloid tissue.
Detailed description
Dysregulation of several intracellular pathways have been reported by various investigators.
[A] Dysregulated apoptosis pathway: p53 mutations have been found in both hypertrophic scar and keloids fibroblasts from cultured cells to various extents. p53 plays a central role in the DNA damage response by inducing cell cycle arrest and/or apoptotic cell death. Time course experiments making cell cultures at different times to investigate the phenomenon of apoptosis and its involvement in the process of pathological scarring in both hypertrophic scars and keloid indicate to dysregulation of apoptotic pathways in Keloid tissue.
[B]Dysregulated TGF- β signaling: Transforming growth factor- β1 (TGF- β1) is well known as the crucial fibrogenic cytokine promoting ECM production and tissue fibrosis in keloid forming [9]. TGF- β1 is an essential profibrotic cytokine for collagen synthesis, and it is well known to increase mRNA expression of procollagen I. Administration of TGF- β1 resulted in a dramatic increase in intracellular collagen I levels in keloid fibroblasts. Due to the close relationship between TGF- β signaling and the production of collagen, blocking TGF- β signaling has the potential of repressing fibroblast proliferation and collagen synthesis, thereby preventing the formation of keloids.
[C]Dysregulated VEGF signaling pathway: VEGF (Vascular endothelial growth factor), one of the most widely studied secreted factors involved in angiogenesis, has been implicated as crucial to normal and pathological wound healing [18]. Gira et al. [19] indicated that VEGF production is abundant in the underlying dermis of keloids. In vitro studies have indicated that VEGF is expressed at higher levels in keloid-derived Fibroblasts than in normal skin Fibroblasts.
Sorafenib is an orally active multikinase inhibitor and has been reported to be an effective inhibitor of apoptosis, TGF-β signaling and VEGF pathway signaling, making it an ideal drug to test in the setting of extensive keloid disorder.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib arm | Experimental | Drug: SorafenibAll patients will be treated with sorafenib. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Clinical Diagnosis of a keloid.
- Presence of extensive keloid disease as defined in section 1.3
- Age 18 to 50
- A signed informed consent document (ICD)
- Able and willing to receive sorafenib
Key exclusion criteria (17 listed)
- Diastolic Blood pressure of 90 mm Hg or above
- History of any degree of hypertension, even medically controlled hypertension
- History of any form of cardiovascular disease or stroke
- History of any form of thromboembolic event
- History of renal dysfunction or proteinuria,
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 |
|---|---|---|
| SorafenibAlso: Nexavar (sorafenib)Treatment will be administered on an outpatient basis. All patients will keep a drug diary in order to record compliance with their drug regime. Sorafenib will be taken orally. Maximum length of treatment is 6 months. Starting dose of sorafenib is 200 mg three times per week for one month. In absence of Grade 2 toxicity, the dose will be increased on a monthly basis and will stop at 400 mg twice daily. | Drug | Sorafenib arm |
Primary outcome
Response Rate (RR) of extensive keloids to sorafenib. RR is the sum of Complete Remission (CR) and Partial Remission (PR) at 12 month after last dose of sorafenib.
Time frame: 12 months
The primary objective of this trial is to demonstrate the efficacy of sorafenib in patients with extensive keloids.
1 secondary outcome
The secondary endpoint of this trial is to demonstrate the rate of AE and SAE following exposure to sorafenib measured while on treatment as well as at 1 year after the last dose of sorafenib.
Time frame: 12 months
Results and safety
The study was stopped early (reason given: IND application was not approved by the US FDA - Project was never started). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2016.
Related trials for Keloids
Not yet recruiting
Fractional Radiofrequency With Streroids Versus Fractional CO2 Laser With Steroids in the Treatment of Keloids
Keloids
Active, not recruiting
Transdermal Versus Intralesional Betamethasone for Keloids
Keloid
RecruitingPhase 2
Ritlecitinib in Patients With Keloids or Those Undergoing Keloidectomy
Keloid
Recruiting
Radiotherapy for Keloids
Keloid
RecruitingObservational study
Keloid Pathogenesis And Fibroblast Activation Study
Keloids, Fibroblast
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.
Michael H Tirgan, MD principal investigator
St. Luke's Roosevelt Hospital Center, New York City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib in people with Keloids, run by Tirgan, Michael H., M.D. at 1 site in United States.
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 8 inclusion and 17 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: stopped early, as of the sponsor's last update on 18 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
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 was stopped early (reason given: IND application was not approved by the US FDA - Project was never started). Results are not available in the source record.
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.
What does the primary outcome measure?
Response Rate (RR) of extensive keloids to sorafenib. RR is the sum of Complete Remission (CR) and Partial Remission (PR) at 12 month after last dose of sorafenib. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Oct 2016.