Phase II Trial to Evaluate the Efficacy of Topical Bexarotene Gel in Patients With Parapsoriasis

Parapsoriasis Clinical Trial

Official title:

A Phase II Trial to Evaluate the Efficacy of Topical Bexarotene Gel in Patients With Parapsoriasis: a Topical Chemoprevention Strategy for Cutaneous T-cell Lymphoma.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00322296
• Other study ID #: 00-031
• Status: Terminated
• Phase: Phase 2
• First received: May 4, 2006
• Last updated: April 15, 2013
• Start date: April 2001
• Est. completion date: August 2004

Study information

• Verified date: May 2006
• Source: Fox Chase Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Parapsoriasis is a term that refers to a precursor stage of cutaneous T-cell lymphoma (CTCL)/mycosis fungoides(MF). Complete responses (clearing) of early presentations of CTCL/MF have been shown to be associated with long-term survival and cure. Induction of a complete response in parapsoriasis, therefore, would seem to be a desirable therapeutic endpoint. Bexarotene 1% gel has been approved for treatment of cutaneous T-cell lymphoma (mycosis fungoides). The goal of this study is to evaluate the tolerability, safety and efficacy of bexarotene 1% gel in patients with parapsoriasis.

Description:

Parapsoriasis is a term that refers to a red, scaling (papulosquamous) eruption on the skin characterized by its distribution (trunk and proximal extremities), asymptomatic nature and chronic course. Histologically, parapsoriasis is characterized by variable degrees of parakeratosis and epidermal spongiosis with a superficial, sparse, patchy, lichenoid infiltrate of lymphocytes and varying degrees of epidermal involvement (epidermotropism). No definitive studies have defined its etiology or epidemiology.

Historically, the term "parapsoriasis" was introduced into the dermatology literature by Brocq in 1902. Brocq used the term to clinically characterize a variety of papulosquamous eruptions that were first reported in the late 19th century. In 1905, he attempted to categorize parapsoriasis in relationship to other papulosquamous diseases of the skin. In his model, Brocq delineated a relationship between some variants of parapsoriasis (parapsoriasis en plaques or large plaque parapsoriasis) and mycosis fungoides or cutaneous T-cell lymphoma (CTCL). The first cases of mycosis fungoides (MF) were reported early in the 19th century. Progressive stages of MF ("premycotic" patch phase, plaque phase and tumor phase) were defined later in the 19th century, while the neoplastic nature of the disease remained unknown. Brocq's model sought to emphasize clinical similarities between some variants of parapsoriasis (large plaque) and early, patch phase MF.

Immunohistochemical (IHC) studies have demonstrated that parapsoriasis shares a similar immunophenotype with early stage CTCL in that the lymphocytic infiltrate is predominantly composed of CD4 lymphocytes. Polymerase chain reaction (PCR)- based T-cell receptor (TCR) gene rearrangement studies have demonstrated that parapsoriasis is a lymphoproliferative disorder characterized by the detection of clonal populations of T-cells, as is CTCL. Knowledge of the natural history of parapsoriasis stems from a series of longitudinal outcome studies published over the last 40 years. Progression to unequivocal CTCL ranged from 0% to 35% of parapsoriasis cases. Typically, cases associated with progression to CTCL tend to have larger plaques with clinical features of atrophy and/or poikiloderma.

Based on the clinicopathologic similarities of parapsoriasis and early stage CTCL, the exact nosology of parapsoriasis has been challenged, with a hypothesis that all variants of parapsoriasis (large plaque, small plaque and digitate) are synonymous with early MF. Nevertheless, parapsoriasis is recognized as a distinct precursor stage (T0N0M0) in the TNM staging schema of CTCL. T0 CTCL is defined by the presence of lesions clinically and/or histologically suggestive of CTCL.

No definitive studies have been published regarding therapy of parapsoriasis. When treated, most patients are initiated empirically on topical steroids or phototherapy. Typically, patients will have partial responses and/or relapse off any therapy. A rational therapeutic strategy for parapsoriasis is lacking because there are no longitudinal studies that correlate treatment response and impact on progression to CTCL.

Bexarotene is a resinoid, a subclass of retinoids that binds preferentially to nuclear retinoic X receptors (RXR), and has therapeutic activity in CTCL. Bexarotene 1% gel has been approved for treatment of CTCL and found to have up to a 63% response rate in Stage Ia to IIa CTCL. The goal of this study was to evaluate the tolerability, safety and efficacy of bexarotene 1% gel in patients with parapsoriasis and to evaluate the anti-tumor host response in pre- and post-treatment skin biopsies.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: August 2004
• Est. primary completion date: July 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A clinical and histologic diagnosis of parapsoriasis (T0 CTCL)

• Age 18 years or older.

• Acceptable laboratory studies

• Must be free of serious concurrent illness.

• Women of child-bearing potential must have negative serum pregnancy test prior to the initiation of treatment.

Exclusion Criteria:

• Topical or systemic therapies within four weeks of entry in the study.

• Participation in any other investigational drug study within thirty days of entry in this study.

• Oral retinoid therapy for any indication within three months of entry in the study.

• Participation in any other study using topical retinoid therapy.

• Pregnancy or active breast-feeding.

• Serious known concurrent medical illness or infection.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma, T-Cell, Cutaneous
• Parapsoriasis

Intervention

Drug:
• Bexarotene 1% gel

Locations

Country	Name	City	State
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Fox Chase Cancer Center	Ligand Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary efficacy endpoints (outcome) are the skin lesion responses determined by the Composite Assessment of Index Lesion Disease Severity following up to sixteen weeks of treatment
Secondary	Secondary efficacy endpoints (outcomes) include the disease response to treatment as determined by percentage of total body surface area involvement and physician global assessment following up to sixteen weeks of treatment.
Secondary	Also, antitumor host response as determined by immunohistochemistry in pre and post treatment skin biopsies.