Safety, Tolerability, and Efficacy Study of CLL442 in Patients With Cutaneous Squamous Cell Carcinoma in Situ (SCCis)

Study Overview
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Brief Summary
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The purpose of this first in human and proof of concept study is to characterize the safety, tolerability and initial efficacy of CLL442 in patients with Squamous Cell Carcinoma in situ (SCCis) to enable further clinical development of CLL442.

Official Title
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A Randomized Investigator and Patient Blind Placebo-controlled Parallel Group First in Human and Proof of Concept Study to Evaluate the Safety Tolerability and Efficacy of CLL442 in Patients With Cutaneous Squamous Cell Carcinoma in Situ

Conditions
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Cutaneous Squamous Cell Carcinoma in Situ (CSCCis)

Intervention / Treatment
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* Drug: Cutaneous Cream application
* Drug: Placebo Cutaneous Cream application


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent has been obtained. Male and female patients, age ≥ 18 to ≤ 90 years (at the time of the screening visit). A primary, clinically diagnosed and histologically confirmed cutaneous SCC in situ lesion, with or without the involvement of the follicular unit, and histologically diagnosed within 30 days of the screening visit. The post-biopsy residual SCCis lesion must be visually evident and at least 3 mm in either length or width. The lesion must be located in a place easily accessible for topical application by the patient or their caregiver, excluding the genitals, perianal area, sub-ungual area, eyelids, ear and must be >1 cm away from the eyes and mouth. Exclusion Criteria: Evidence of dermatological disease or histological evidence of a confounding skin condition in the treatment area, including but not limited to BCC, worse level/grade of SCC, rosacea, psoriasis, atopic dermatitis, eczema, xeroderma pigmentosa, verrucous lesions or any other tumor in the biopsy specimen. Lesions with atypical histology such as: spindle cell SCC, acantholytic SCC, clear cell SCC, adenosquamous SCC, desmoplastic SCC or lesions that have been present for a short time and have been fast growing. Treatment of the target SCCis lesion within 8 weeks of screening visit by any of the following treatments: Liquid nitrogen, Photochemotherapy (PUVA), Long wave ultra violet radiation (UVB light), surgical excision or curettage within 1 cm of target lesion.; Systemic retinoids.; Ionizing radiation or interlesional injections or; Undergone a facial resurfacing procedure, i.e., chemical peel, laser resurfacing, dermabrasion, within the target lesion; Treatment with the following topical agents within the 4 weeks prior to the screening visit: Levulanic acid, 5-fluorouracil, corticosteroids, retinoids, diclofenac, hyaluronic acid, imiquimod. History of recurrence of the target SCCis lesion. Systemic use of immunosuppressive drugs within 4 weeks prior to screening visit or during the treatment period - Photodynamic therapy or immunomodulators, cytotoxic drugs, or interferon/interferon inducers within 4 weeks prior to study entry or expected during the study. Women of child-bearing potential, unless they are using at least basic methods of contraception during dosing of investigational drug. Pregnant or nursing (lactating) women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A first in human,proof of concept study. The study is investigator-and patient-blinded, randomized, placebo-controlled study in patients with SCCis, to assess safety, tolerability and initial efficacy of CLL442 after up to 84 days twice daily application of CLL442 or placebo on one lesion.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLL442<br>Cutaneous Cream application twice daily | Drug: Cutaneous Cream application<br>* Cutaneous Cream application twice daily with experimental (CLL442)<br>|
| Placebo Comparator: Placebo<br>Placebo Cutaneous Cream application twice daily | Drug: Placebo Cutaneous Cream application<br>* Cutaneous Cream application twice daily with placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AE), serious adverse events (SAEs) of CLL442 on lesion free skin at Day 7 | As part of safety and tolerability assessment, assess the incidence of adverse events (AE), serious adverse events (SAEs) in patients with SCCis treated with CLL442 or placebo on lesion free skin for 7 days | Day 7 | 
| Change in the size of One SCCis lesion area at Day 84 from Day 1 | Area is measured by pen and ruler and standardized digital photography | Day 1 and Day 84 | 
| Change in the Local skin reactions severity score at Day 7 or Day 84 from Day 1 | Local skin reactions severity score | Day 1, Day 7, Day 84 | 
| Incidence of adverse events (AE), serious adverse events (SAEs) of CLL442 on SCCis lesion at Day 84 | As part of safety and tolerability assessment, assess the incidence of adverse events (AE), serious adverse events (SAEs) in patients with SCCis treated with CLL442 or placebo on SCCis lesion area for 84 days. | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CLL442 plasma concentration | To evaluate the systemic pharmacokinetics of CLL442 | Day 1 through Day 84 | 
| Time required to achieve 50% decrease in 1 lesion area. | Part of efficacy assessment. | 84 days | 
| Time required to achieve complete SCCis 1 lesion clearance (censored by end of study visit). | Part of efficacy assessment. | 84 days | 
| Percentage of pts with complete clearance at the end of the study, assessed visually and histologically | Part of efficacy assessment. | 84 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cutaneous Squamous Cell Carcinoma (cSCC) in situ, mTOR kinase inhibitors, PI3K inhibitor.