Topical Laser-assisted Combination Chemotherapy for Basal Cell Carcinoma- a Clinical Study

• ClinicalTrials.gov Identifier: NCT03541252
• Recruitment Status: Completed
• First Posted: May 30, 2018
• Last Update Posted: October 14, 2020
• Sponsor: Merete Haedersdal
• Information provided by (Responsible Party): Merete Haedersdal, Bispebjerg Hospital

Study Description

Brief Summary:

A prospective clinical, uncontrolled, open-label, explorative phase IIa trial on patients with histologically- confirmed superficial and nodular basal cell carcinoma (BCC) . The study assesses tolerability and tumor clearance after laser-assisted topical delivery of two synergistic chemotherapeutic agents, cisplatin and 5-fluorouracil (5-FU) in BCC patients.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Basal Cell	Drug: AFL-assisted cisplatin+5-FU	Phase 1; Phase 2

Detailed Description:

Patients will receive ablative fractional laser (AFL)-assisted cisplatin+5-fluorouracil (5-FU) as a treatment for their cutaneous basal cell carcinoma (BCC). In brief, treatment areas consisting of tumors and a 5 mm margin will undergo AFL exposure (CO2 laser) followed by 60 min topical application of a marketed and commercially available IV cisplatin solution (0.1%) at a dose of 0.25 ml per cm2. After removal of cisplatin, a commercially distributed 5-FU cream (5% Efudix®) will be applied to the treatment area at a dose of 0.125 ml per cm2 and left under occlusion. After skin evaluations on Day 1 and 5 after treatment, the same 5-FU dose will be applied, again left under occlusion. In total, 5-FU will remain on the skin for 7 days after AFL treatment whereafter it will be washed off.

An additional repeat AFL-cisplatin+5-FU treatment on Day 30 will be offered if tumors persist, based on clinical evaluation and imaging on Day 30.

Outcome measures and methods/techniques are summarized below.

Primary outcome:

To investigate tolerability of topical AFL-assisted cisplatin+5-FU therapy for BCC by evaluating:

I. Severity and duration of clinical local skin reactions including erythema, edema, scabbing, flaking and pustulation assessed by a physician using an established 0-4 point scale (none, mild, moderate, severe) from 0-30 days post-treatment.

II. Occurrence of side effects (prolonged erythema/edema, hyper/hypopigmentation, scarring and infection) up to 3 months post-treatment.

Secondary outcome:

1) To monitor BCC tumor size and clearance based on clinical assessments and dermoscopy, supported by non-invasive imaging techniques including dynamic optical coherence tomography (D-OCT), reflectance confocal microscopy (RCM), high intensity focused ultrasound (HIFU) and histological analysis up to 3 months post-treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A prospective clinical, uncontrolled, open-label, explorative phase IIa trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tolerability of Laser-assisted Cisplatin + 5-fluorouracil- an Exploratory Proof of Concept Study of Topical Combination Chemotherapy for Basal Cell Carcinoma
• Actual Study Start Date: March 9, 2018
• Actual Primary Completion Date: September 2, 2019
• Actual Study Completion Date: September 2, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Basal Cell Carcinoma Patients; Patients (>18 years) with histologically-verified superficial or nodular basal cell carcinoma (<20 mm on the face/scalp, <50mm on the trunk/extremities)

Drug: AFL-assisted cisplatin+5-FU; Patients will receive AFL-assisted cisplatin+5-FU as a treatment for their BCC. In brief, treatment areas consisting of tumors and a 5 mm margin will undergo CO2 laser exposure followed by 60 min topical application of a marketed and commercially available IV cisplatin solution (0.1%) After removal of cisplatin, a commercially distributed 5-FU cream (5%) will be applied to the treatment area at a dose of 0.125 ml per cm2 and left under occlusion. After skin evaluations on Day 1 and 5 after treatment, the same 5-FU dose will be applied, again left under occlusion. In total, 5-FU will remain on the skin for 7 days after AFL treatment whereafter it will be washed off. An additional repeat AFL-cisplatin+5-FU treatment on Day 30 will be offered if tumors persist, based on clinical evaluation and imaging on Day 30.

Outcome Measures

Primary Outcome Measures :

1. Change in Occurence of Local Skin Side Effects [ Time Frame: Baseline-3 months post treatment ]
   Non-blinded, clinical evaluation of local erythema, edema, flaking, crusting/scabbing, pustulation, scarring, hypo/hyperpigmentation, infection in treated areas will be performed by a physician using a FDA-approved 0-4 point LSR scale at Days 1, 5, 14, 30 and 3 months after AFL exposure. Standardized, clinical photographs are taken to document skin reactions at each visit.

Secondary Outcome Measures :

1. Tumor Response- Clinical [ Time Frame: baseline-3 months post treatment ]
   Tumor size (mm) and clearance (yes or no) will be evaluated clinically at baseline, Day 30 and Month 3. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines.
2. Tumor Response- Imaging [ Time Frame: baseline-3 months post treatment ]
   Tumor size (mm) and clearance (yes or no) will be evaluated using non-invasive dynamic optical coherence tomography, high-intensity focused ultrasound and reflectance confocal microscopy imaging at baseline, Day 30 and Month 3. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines.
3. Tumor Response- Histological Clearance [ Time Frame: 3 months post treatment ]
   Histological verification of tumor clearance will be performed 3 months after first treatment using tissue sections from a 4 mm punch biopsy. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Histologically-verified, previously untreated superficial or nodular BCCs on the scalp, face, extremities or trunk
2. >18 years of age at baseline
3. Legally competent, able to give verbal and written informed consent
4. Subject in good general health, is willing to participate and can comply with protocol requirements.
5. Fitzpatrick skin phototype I-III
6. Female subjects of childbearing potential1 must be confirmed not pregnant by a negative urine pregnancy test prior to trial treatment.

Exclusion Criteria:

1. High-risk BCC i. Tumors in the following anatomical locations: midface, orbital, ears ii. Size: >20 mm in facial/scalp areas or > 50 mm in non-facial/non-scalp areas iii. Subtype: morpheaform and micronodular BCC iv. History: Gorlin syndrome or immunosuppression
2. Previous treatment of the BCC lesion
3. Known allergy to cisplatin or Efudix®
4. Other skin diseases present in the treatment area
5. Tattoo in the treatment area which may interfere with or confound evaluation of the study
6. History of keloids which is deemed clinically relevant in the opinion of the investigator
7. Fitzpatrick skin phototype IV-VI
8. Lactating or pregnant women

Contacts and Locations

Locations

Denmark

Department of Dermatology, Bispebjerg Hospital

Copenhagen, Hovedstaden, Denmark, 2400

Sponsors and Collaborators

Merete Haedersdal

More Information

• Responsible Party: Merete Haedersdal, Professor, Senior Consultant, PhD, DMSc, Bispebjerg Hospital
• ClinicalTrials.gov Identifier: NCT03541252
• Other Study ID Numbers: EudraCT2018-000141-39
• First Posted: May 30, 2018
• Last Update Posted: October 14, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Basal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Cisplatin; Antineoplastic Agents