Laser Immunotherapy With and Without Topical Anti-PD1 in Basal Cell Carcinomas

Laser Immunotherapy With and Without Topical Anti-PD1 in Basal Cell

The study aim is to assess the immunological and clinical response in basal cell carcinoma (BCC) treated with ablative fractionated laser (AFL) as monotherapy and compare with BCC treated with combination-therapy of AFL and the anti-PD1-drug nivolumab and with nivolumab as monotherapy.

Study Overview

• Status: Unknown
• Conditions: Immune Response; Immunotherapy; BCC - Basal Cell Carcinoma; Ablative Fractionated Laser
• Intervention / Treatment: Device: Ablative fractionated laser; Drug: Nivolumab 10 MG/ML

Detailed Description

Explorative open label study. Patients and investigators are non-blinded and patients not randomized to interventions.

Three intervention groups:

1. AFL monotherapy (8-10 patients)
2. AFL+intratumoral nivolumab (8-10 patients)
3. Intratumoral nivolumab monotherapy (8-10 patients)

Patients will attend 4 visits Immunological response is determined by immunohistochemistry (IHC) analysis from biopsies taken prior to AFL, AFL+Nivolumab or Nivolumab treatment (baseline) and compared with biopsies 1 week after treatment. Further, comparison of the immunological response of AFL monotherapy with immunological response AFL+Nivolumab and Nivolumab as monotherapy will be performed.

Patients included for AFL as monotherapy will after tumor demarcation receive AFL of the BCC including a 5 mm margin. An occlusive bandage will be applied to the treated area and is to be removed by the patient 24 hours after treatment or after end of secretion/oozing from the treated area.

Patients included for AFL+Nivolumab will after tumor demarcation receive AFL of the BCC including a 5 mm margin, immediately followed by intratumoral injection of Nivolumab. An occlusive bandage will be applied to the treated area and is to be removed by the patient 24 hours after treatment or after end of secretion/oozing form the treated area.

Patients included for monotherapy with Nivolumab will after tumor demarcation get an intratumoral injection of Nivolumab. An occlusive bandage will be applied to the treated area and is to be removed by the patient 24 hours after treatment or after end of secretion from the treated area.

All patients will have a final visit at week 15, around 12 weeks after first treatment, where the clinical response will be evaluated, and treated tumor will be treated following national guidelines for treatment of BCCs.

For subgroups of clinical responders and non-responders tumor will at week 15 be used for multiplex gene expression analysis via nanostring (Pan cancer immune profiling panel).

For all groups, clinical photographs are taken at every study visit. For patients that present with more than one tumor, patients will be invited to participate with all tumors relevant to the study.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Recruiting
    • Department of Dermatology
    • Contact: Silje Omland, MD; Phone Number: +4524402485; Email: silje.haukali.omland.01@regionh.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients 18 years or older
• Clinical suspicion of BCC or histologically verified BCC at baseline and histologically verified BCC at visit 2, irrespective of histologic subtype with diameter ≥7 mm at baseline.
• Signed informed consent.
• Female subjects of childbearing potential* must be confirmed not pregnant by a negative pregnancy test prior to study treatment and must use a safe contraceptive method

Exclusion Criteria:

• Concomitant treatment with 5-FU or imiquimod
• Concomitant chemotherapeutic treatment
• Concomitant systemic immunotherapeutic treatment, including Prednisolone
• Pregnant or lactating women
• Allergies to anti-PD1
• Patients with a tendency to form keloids
• Other skin diseases or tattoos in the treatment area

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AFL monotherapy; Singe dose AFL as monotherapy, 100 mJ	Device: Ablative fractionated laser; Se previously
Active Comparator: AFL+nivolumab; Single dose AFL 100 mJ followed by immediate intratumoral injection of nivolumab 10% 0.1 ml/cm2 tumor	Device: Ablative fractionated laser; Se previously; Drug: Nivolumab 10 MG/ML; Se previously; Other Names: opdivo
Active Comparator: nivolumab monotherapy; Intratumoral injection of nivolumab 10% 0.1 ml/cm2 tumor	Drug: Nivolumab 10 MG/ML; Se previously; Other Names: opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunological response of AFL and nivolumab as monotherapy and AFL+Nivolumab in BCC	IHC as; CD8/CD3 ratio; CD4+Foxp3+/CD4 ratio	1 week
investigate the clinical response of AFL and Nivolumab as monotherapy and AFL+Nivolumab in BCC	evaluated by tumor reduction measured in mm and documented by clinical photos	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of AFL, intratumoral nivolumab and AFL+Nivolumab	evaluated as local skin reactions 1 week and 12 weeks after exposure	12 weeks
Detection of intra-tumoral Nivolumab	evaluated by ELISA with anti-anti-PD1	1 week
Analysis and quantification of PD-L1 expression (tumor cells and TILs)	evaluated by IHC	2 weeks

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: September 22, 2020
• First Submitted That Met QC Criteria: September 29, 2020
• First Posted (Actual): September 30, 2020

Study Record Updates

• Last Update Posted (Actual): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 29, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: Eudra-CT: 2019-003310-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Not yet decided

Drug and device information, study documents

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