Carcinoma, Basal Cell
Conditions
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.
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.
Interventions
DRUGAFL-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.
Sponsors
Merete Haedersdal
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A prospective clinical, uncontrolled, open-label, explorative phase IIa trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Occurence of Local Skin Reaction (LSR) Side Effects TOTAL COMPOSITE SCORE | Days 1, 3-5, 14, 30 and 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 LSR scale at Days 1, 3-5, 14, 30 and 3 months after AFL exposure. Each parameter was graded on a standardized 5-point severity scale (0-4) representing none, mild, moderate, prominent, and severe. A total composite score reflecting overall LSR severity was then calculated based on the sum of all parameters (minimum score 0- least severe; max score: 24-most severe). lower scores are better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response- Clinical Clearance Determined by Clinical Assessment by Physician | Day 30 and Month 3 post treatment | Tumor clearance (yes or no) will be evaluated clinically at Day 30 and Month 3. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines.¨ |
| Imaging-based Tumor Response: Complete Tumor Clearance Determined by Physician Performing Imaging | Day 30 and 3 months post treatment | Clearance (yes or no) will be evaluated using non-invasive dynamic optical coherence tomography, high-intensity focused ultrasound and reflectance confocal microscopy imaging at Day 30 and Month 3. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines. |
| Tumor Response- Histological Tumor Clearance Determined by Pathologist | 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. NOTE: Overall Number of Participants Analyzed is not consistent with numbers provided in any of the rows in the Participant Flow module since only 18 of the 19 patients consented to undergoing histologicla verification with biopsy. Those, presented data represents patients that underwent biopsy at the 3 month mark. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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)
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. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Basal Cell Carcinoma Patients | — |
|---|---|---|
| Age, Continuous | 73 years | — |
| Histological Tumor Subtype Nodular BCC | 13 Tumors | — |
| Histological Tumor Subtype Superficial BCC | 6 Tumors | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 5 Participants | — |
| Sex: Female, Male Male | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Change in Occurence of Local Skin Reaction (LSR) Side Effects TOTAL COMPOSITE SCORE
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 LSR scale at Days 1, 3-5, 14, 30 and 3 months after AFL exposure. Each parameter was graded on a standardized 5-point severity scale (0-4) representing none, mild, moderate, prominent, and severe. A total composite score reflecting overall LSR severity was then calculated based on the sum of all parameters (minimum score 0- least severe; max score: 24-most severe). lower scores are better.
Time frame: Days 1, 3-5, 14, 30 and 3 months post treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Basal Cell Carcinoma Patients | Change in Occurence of Local Skin Reaction (LSR) Side Effects TOTAL COMPOSITE SCORE | Day 1 post treatment | 7 score on a scale |
| Basal Cell Carcinoma Patients | Change in Occurence of Local Skin Reaction (LSR) Side Effects TOTAL COMPOSITE SCORE | Day 3-5 post treatment | 9 score on a scale |
| Basal Cell Carcinoma Patients | Change in Occurence of Local Skin Reaction (LSR) Side Effects TOTAL COMPOSITE SCORE | Day 30 post treatment | 4 score on a scale |
| Basal Cell Carcinoma Patients | Change in Occurence of Local Skin Reaction (LSR) Side Effects TOTAL COMPOSITE SCORE | Month 3 post treatment | 2 score on a scale |
Secondary
Imaging-based Tumor Response: Complete Tumor Clearance Determined by Physician Performing Imaging
Clearance (yes or no) will be evaluated using non-invasive dynamic optical coherence tomography, high-intensity focused ultrasound and reflectance confocal microscopy imaging at Day 30 and Month 3. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines.
Time frame: Day 30 and 3 months post treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Basal Cell Carcinoma Patients | Imaging-based Tumor Response: Complete Tumor Clearance Determined by Physician Performing Imaging | Day 30 | 13 Participants |
| Basal Cell Carcinoma Patients | Imaging-based Tumor Response: Complete Tumor Clearance Determined by Physician Performing Imaging | Month 3 | 18 Participants |
Secondary
Tumor Response- Clinical Clearance Determined by Clinical Assessment by Physician
Tumor clearance (yes or no) will be evaluated clinically at Day 30 and Month 3. If residual tumor is identified at 3 months follow-up, patients will receive conventional treatment according to national guidelines.¨
Time frame: Day 30 and Month 3 post treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Basal Cell Carcinoma Patients | Tumor Response- Clinical Clearance Determined by Clinical Assessment by Physician | Clinical Clearance Day 30 | 13 Participants |
| Basal Cell Carcinoma Patients | Tumor Response- Clinical Clearance Determined by Clinical Assessment by Physician | Clinical Clearance Month 3 | 18 Participants |
Secondary
Tumor Response- Histological Tumor Clearance Determined by Pathologist
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. NOTE: Overall Number of Participants Analyzed is not consistent with numbers provided in any of the rows in the Participant Flow module since only 18 of the 19 patients consented to undergoing histologicla verification with biopsy. Those, presented data represents patients that underwent biopsy at the 3 month mark.
Time frame: 3 months post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Basal Cell Carcinoma Patients | Tumor Response- Histological Tumor Clearance Determined by Pathologist | 17 Participants |