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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cutaneous Squamous Cell Carcinoma in Situ (CSCCis)
• Intervention / Treatment: Drug: Cutaneous Cream application; Drug: Placebo Cutaneous Cream application

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Phillip, Australian Capital Territory, Australia, 2606
      • Novartis Investigative Site
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Novartis Investigative Site
  • California
    • Fountain Valley, California, United States, 92708
      • Novartis Investigative Site
  • Florida
    • Gainesville, Florida, United States, 32606
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLL442; Cutaneous Cream application twice daily	Drug: Cutaneous Cream application; Cutaneous Cream application twice daily with experimental (CLL442)
Placebo Comparator: Placebo; Placebo Cutaneous Cream application twice daily	Drug: Placebo Cutaneous Cream application; Cutaneous Cream application twice daily with placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful 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 record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: November 3, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Cutaneous Squamous Cell Carcinoma (cSCC) in situ, mTOR kinase inhibitors, PI3K inhibitor.
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma in Situ; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: CCLL442X2201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No