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Sorafenib for Patients With Extensive Keloids

Primary Purpose

Keloids

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sorafenib

About this trial

This is an interventional treatment trial for Keloids focused on measuring Keloid, Patient who have extensive or massive keloids

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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
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

Sites / Locations

Michael H. Tirgan, MD

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib arm

Arm Description

All patients will be treated with sorafenib.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01425216

First Posted

August 19, 2011

Last Updated

October 17, 2016

Sponsor

Tirgan, Michael H., M.D.

1. Study Identification

Unique Protocol Identification Number

NCT01425216

Brief Title

Sorafenib for Patients With Extensive Keloids

Official Title

Phase II Trial of Sorafenib in Patients With Extensive Keloids

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Terminated

Why Stopped

IND application was not approved by the US FDA - Project was never started

Study Start Date

March 2013 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tirgan, Michael H., M.D.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Keloids

Keywords

Keloid, Patient who have extensive or massive keloids

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib arm

Arm Type

Experimental

Arm Description

All patients will be treated with sorafenib.

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

Nexavar (sorafenib)

Intervention Description

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.

Primary Outcome Measure Information:

Title

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.

Description

The primary objective of this trial is to demonstrate the efficacy of sorafenib in patients with extensive keloids.

Time Frame

12 months

Secondary Outcome Measure Information:

Title

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.

Description

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. - Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael H Tirgan, MD

Organizational Affiliation

St. Luke's Roosevelt Hospital Center, New York City

Official's Role

Principal Investigator

Facility Information:

Facility Name

Michael H. Tirgan, MD

City

New York

State/Province

New York

ZIP/Postal Code

10023

Country

United States

12. IPD Sharing Statement

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Sorafenib for Patients With Extensive Keloids

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