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

NCT03333694 | Terminated Phase 1 FDA Drug

• 1 other identifier: CCLL442X2201
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 8

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.

Conditions

Cutaneous Squamous Cell Carcinoma in Situ (CSCCis)

Keywords

Cutaneous Squamous Cell Carcinoma (cSCC) in situ, mTOR kinase inhibitors, PI3K inhibitor.

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• CLL442 plasma concentration

  Day 1 through Day 84

• Time required to achieve 50% decrease in 1 lesion area.

  84 days

• Time required to achieve complete SCCis 1 lesion clearance (censored by end of study visit).

  84 days

• Percentage of pts with complete clearance at the end of the study, assessed visually and histologically

  84 days

Study Arms (2)

CLL442

EXPERIMENTAL

Cutaneous Cream application twice daily

Drug: Cutaneous Cream application

Placebo

PLACEBO COMPARATOR

Placebo Cutaneous Cream application twice daily

Drug: Placebo Cutaneous Cream application

Interventions

Cutaneous Cream application DRUG

Cutaneous Cream application twice daily with experimental (CLL442)

CLL442

Placebo Cutaneous Cream application DRUG

Cutaneous Cream application twice daily with placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

Novartis Investigative Site

Phoenix, Arizona, 85032, United States

Location

Novartis Investigative Site

Fountain Valley, California, 92708, United States

Location

Novartis Investigative Site

Gainesville, Florida, 32606, United States

Location

Novartis Investigative Site

Phillip, Australian Capital Territory, 2606, Australia

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Benowa, Queensland, 4217, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Related Links

• Results for CCLL442X2201 can be found on the Novartis Clinical Trial Results Website
• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: investigator and patient blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: November 7, 2017
• Study Start: December 15, 2017
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: December 11, 2020

Record last verified: 2020-09

Locations

US (3); AU (3); BE (2)