Clinical trial NCT04570683: Laser Immunotherapy With and Without Topical Anti-PD1 in Basal Cell Carcinomas
Official title: Laser Immunotherapy With and Without Topical Anti-PD1 in Basal Cell
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: BCC - Basal Cell Carcinoma
Immune Response
Immunotherapy
Ablative Fractionated Laser
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: immunological response of AFL and nivolumab as monotherapy and AFL+Nivolumab in BCC
timeFrame: 1 week
measure: investigate the clinical response of AFL and Nivolumab as monotherapy and AFL+Nivolumab in BCC
timeFrame: 12 weeks
Secondary outcomes:
measure: Tolerability of AFL, intratumoral nivolumab and AFL+Nivolumab
timeFrame: 12 weeks
measure: Detection of intra-tumoral Nivolumab
timeFrame: 1 week
measure: Analysis and quantification of PD-L1 expression (tumor cells and TILs)
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Dermatology
Study officials:
References: