Clinical trial NCT03333694: Safety, Tolerability, and Efficacy Study of CLL442 in Patients With Cutaneous Squamous Cell Carcinoma in Situ (SCCis)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cutaneous Squamous Cell Carcinoma in Situ (CSCCis)
Keywords: Cutaneous Squamous Cell Carcinoma (cSCC) in situ, mTOR kinase inhibitors, PI3K inhibitor.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent has been obtained.
2. Male and female patients, age ≥ 18 to ≤ 90 years (at the time of the screening visit).
3. 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.
4. 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:

1. 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.
2. 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;
3. 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.
4. History of recurrence of the target SCCis lesion.
5. 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.
6. Women of child-bearing potential, unless they are using at least basic methods of contraception during dosing of investigational drug.
7. Pregnant or nursing (lactating) women.

Primary outcomes:
measure: Incidence of adverse events (AE), serious adverse events (SAEs) of CLL442 on lesion free skin at Day 7
timeFrame: Day 7
measure: Change in the size of One SCCis lesion area at Day 84 from Day 1
timeFrame: Day 1 and Day 84
measure: Change in the Local skin reactions severity score at Day 7 or Day 84 from Day 1
timeFrame: Day 1, Day 7, Day 84
measure: Incidence of adverse events (AE), serious adverse events (SAEs) of CLL442 on SCCis lesion at Day 84
timeFrame: Day 84
Secondary outcomes:
measure: CLL442 plasma concentration
timeFrame: Day 1 through Day 84
measure: Time required to achieve 50% decrease in 1 lesion area.
timeFrame: 84 days
measure: Time required to achieve complete SCCis 1 lesion clearance (censored by end of study visit).
timeFrame: 84 days
measure: Percentage of pts with complete clearance at the end of the study, assessed visually and histologically
timeFrame: 84 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Fountain Valley
country: United States
facility: Novartis Investigative Site
state: California
city: Gainesville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Phillip
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Benowa
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: