Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Musculoskeletal Diseases

Mouth and Tooth Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Syndrome

Carcinoma

Skin Neoplasms

Carcinoma, Basal Cell

Basal Cell Nevus Syndrome

Nevus, Pigmented

Nevus

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Basal Cell

Skin Diseases

Nevoid Basal Cell Carcinoma Syndrome

Administer nano pulse to lesion for varying time intervals.

PulseCure 100 ns pulse generator: generates 30 kV/cm electric pulses 100 ns long to trigger apoptosis in cells between the electrodes.

NanoBlate: Delivery device to treat 5 mm wide skin lesions with 100 ns pulses from PulseCure

PulseCure pulse generator and Derm-pulse electrode

Ervin E Epstein, MD

Human Basal Cell Carcinomas (BCCs) can be ablated by treating them with nanosecond pulsed electric fields (nsPEF)

The purpose of this study is to determine if low energy, non-thermal, 100 ns pulses can ablate BCCs. The investigators consider this a non-significant risk study because our PulseCure system only applies 0.4 watts to the skin compared to the 40 watts applied by the currently used electrosurgical unit to remove skin lesions, the Hyfrecator. Since the PulseCure applies 1/100 of the energy and does not even heat the skin significantly, it represents a non-significant risk to the patient. Our study will provide the first data on the response of BCCs to these 100 ns pulses. The investigators will first treat three BCCs on BCNS patients with different pulse numbers to determine the pulse number needed to ablate. Once the investigators have the optimal pulse number, the investigators will use it to treat 20 normal patients with sporadic BCCs on their trunks. This should provide sufficient data to conclude whether or not nsPEF can ablate BCCs on normal individuals.

Development of a Nanosecond Pulsed Electric Field System to Treat Skin Cancer

1. Conduct a non-significant risk feasibility clinical trial treating BCCs on the trunk of up to 9 Basal Cell Nevus Syndrome patients with BioElectroMed's PulseCure pulse generator and Derm-Pulse electrode to both demonstrate the safety of nsPEF therapy and identify the optimal pulse number for ablating BCCs.

2. Conduct a non-significant risk Pilot Clinical Trial treating BCCs on the trunk of 20 patients with sporadic BCCs using the optimal pulse number determined from the feasibility trial to assess the efficacy of this technique.

UCSF Benioff Children's Hospital Oakland

receive 150 mg of oral placebo daily for a period of 2 months

receive 150 mg of vismodegib daily for a period of 2 months

Pulse therapy pattern of 2 months of daily treatment and 2 months of no treatment for 24 months.

Vismodegib

Placebo

Clara Curiel-Lewandroski

This study is a single site double blinded Phase II study to evaluate the chemopreventative effectiveness of vismodegib in the treatment of subjects at high risk for developing basal cell carcinomas (BCC).

The primary objective of this study will be to determine if vismodegib pulse therapy will significantly reduce the incidence of newly diagnosed basal cell carcinomas (BCC) in high risk individuals when compared with placebo, as measured by the incidence of biopsy confirmed BCC over a 24 month period.

The secondary objective will be to determine that there will be no difference in the incidence of newly diagnosed squamous cell carcinomas (SCC) in the same subjects receiving vismodegib treatment when compared with placebo, as measured by the incidence of biopsy confirmed SCC over the same 24 month period.

Vismodegib in Basal Cell Carcinomas (BCC) Chemoprevention

A Placebo Controlled Double-Blind Study to Evaluate the Efficacy of Vismodegib as Chemoprevention of New Bcc Development in High Risk Subjects

Measured by the incidence of biopsy confirmed BCC over a 24 month period

Measured by the incidence of biopsy confirmed SCC over the same 24 month period

University of Arizona

receive 150 mg of oral placebo daily for a period of 2 months

Placebo: Pulse therapy pattern of 2 months of daily treatment and 2 months of no treatment for 24 months.

receive 150 mg of vismodegib daily for a period of 2 months

Vismodegib: Pulse therapy pattern of 2 months of daily treatment and 2 months of no treatment for 24 months.

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Amy Selegue

Early study termination due to low accrual. No data analyzed; no results.

The Effect of Vismodegib Pulse Therapy on the Incidence of Newly Diagnosed Basal Cell Carcinomas (BCC)

The Incidence of Newly Diagnosed Squamous Cell Carcinomas (SCC) in the Same Subjects Receiving Vismodegib Treatment When Compared With Placebo

Overall Study

Dermatologic Agents

All Drugs and Chemicals

Aminolevulinic Acid

Methyl 5-aminolevulinate

Daylight mediated photodynamic therapy

Stine R Wiegell, MD, PhD

Photodynamic Therapy (PDT) is an effective treatment of basal cell carcinomas (BCC) however the inconvenience of clinic attendance and discomfort during therapy are significant drawbacks. The objective of this study is to evaluate the effect of daylight-mediated PDT of BCC.

Treatment of Basal Cell Carcinomas With Methyl Aminolevulinate and Daylight

Bispebjerg Hospital

Hans Christian Wulf

Patidegib gel 2%, applied topically, once daily for 12 weeks (Cohort 1)

Patidegib gel 4%, applied topically, once daily for 12 weeks (Cohort 2)

Vehicle gel, applied topically, once daily for 12 weeks (Cohort 1)

Patidegib gel 2%, applied topically, twice daily for 12 weeks (Cohort 3)

Patidegib gel 4%, applied topically, twice daily for 12 weeks (Cohort 4)

Vehicle gel, applied topically, once daily for 12 weeks (Cohort 2)

Vehicle gel, applied topically, twice daily for 12 weeks (Cohort 3)

Vehicle gel, applied topically, twice daily for 12 weeks (Cohort 4)

Patidegib

Vehicle gel

Ervin Epstein, MD

This is a double-blind, dose escalating, randomized, vehicle-controlled study designed to compare the efficacy and safety of patidegib gel 2% and 4% applied once or twice daily in comparison with that of vehicle in patients with Basal Cell Carcinoma. One investigational center (metasite) in the United States will participate in this study. Approximately 36 subjects who meet the study entry criteria will be enrolled into one of four sequential cohorts. Within each cohort subjects will be randomized in a 2:1 ratio to receive active or vehicle gel.

This is a double-blind, dose escalating, randomized, vehicle-controlled study designed to compare the efficacy and safety of patidegib gel 2% and 4% applied once or twice daily in comparison with that of vehicle. Approximately 36 subjects who meet the study entry criteria will be enrolled into one of four sequential cohorts. As soon as one cohort has been completely enrolled, the next cohort will be enrolled. Each subject will treat no more than two previously untreated biopsy confirmed treatment-targeted nodular BCCs. If the subject has additional non-treatment targeted BCCs they can be treated surgically prior to or during the trial. Within each cohort subjects will be randomized in a 2:1 ratio to receive active or vehicle gel. The sequential cohorts will be:

* Cohort 1: patidegib gel 2% or vehicle, once daily
* Cohort 2: patidegib gel 4% or vehicle, once daily
* Cohort 3: patidegib gel 2% or vehicle, twice daily
* Cohort 4: patidegib gel 4% or vehicle, twice daily

The study drug will be applied topically to the treatment-targeted BCCs and a rim of adjacent skin for 12 weeks. Information on reported and observed adverse events (AEs) will be obtained at each visit. An abbreviated physical examination (PE) will be performed at Baseline and Week 12. The treatment-targeted BCCs will be identified by the Investigator at the Baseline visit and will be circled in ink at Baseline, Weeks 6 and 12 and photographed, and measured at all study visits (Baseline, Weeks 2, 6, 8, 10, and 12). Blood samples for complete blood count and serum chemistry and urine for urinalysis will be collected from subjects at Screening, Week 6, and Week 12. Subjects who terminate study participation early will be asked to complete all Week 12 assessments, as appropriate, prior to commencement of any alternative therapy for BCCs (if possible). Subjects who discontinue from the study during the treatment period will not be replaced.

Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle Applied Once or Twice Daily to Decrease the GLI1 Biomarker in Sporadic Nodular Basal Cell Carcinomas

Double-Blind, Dose Escalating, Randomized, Vehicle-Controlled Proof of Concept Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle Applied Once or Twice Daily to Decrease the GLI1 Biomarker in Sporadic Nodular Basal Cell Carcinomas

The ISGTA is a scale with scores ranging from 0 (clear), 1 (almost clear), 2 (minimal residual tumor), to 3 (clearly visible tumor). The Investigator assessed each Baseline treatment-targeted SEB at Weeks 2, 6, 8, 10, and 12. SEBs were defined as clinically diagnosed BCC 5 to 20 mm in diameter on the face, excluding the nose and periorbital skin, and 9 to 20 mm at sites other than the face. The percentage of Baseline treatment-targeted SEBs evaluated as being clear or almost clear at Week x (Week x = 2, 6, 8, 10, or 12) based on the ISGTA scale was calculated as follows: (Number of baseline treatment-targeted SEBs with ISGTA score of 0 or 1 at Week x) / (Number of Baseline treatment-targeted SEBs) \* 100. Missing data were imputed using LOCF. The percentage of responders achieving clear (0) or almost clear (1) on the ISGTA scale are presented by Week.

SEBs were defined as clinically diagnosed BCC 5 to 20 mm in diameter on the face, excluding the nose and periorbital skin, and 9 to 20 mm at sites other than the face. The percent change in greatest diameters of Baseline treatment-targeted SEBs from Baseline to Week 12 was calculated as follows: (sum \[Baseline\] - sum \[Week 12\] / sum \[Baseline\]) \* 100), where sum = the greatest diameters of treatment-targeted SEBs.

All serious adverse events (SAEs) and all other non-serious adverse events (AEs) regardless of causality are located in the Reported AE Module. The number of AEs (including both serious and non-serious) considered related to study drug by the Investigator are presented below. Treatment-emergent AEs are those with an onset after use of study drug.

GLI1 change is a biomarker of the HH signaling pathway. A change in GLI1 mRNA levels reflect a change in the HH pathway. Surgically eligible basal cell carcinomas (SEBs) were defined as clinically diagnosed basal cell carcinoma (BCC) 5 to 20 millimeters (mm) in diameter on the face, excluding the nose and periorbital skin, and 9 to 20 mm at sites other than the face. A single baseline BCC designated as a treatment-targeted tumor at Baseline was biopsied first at Baseline and again following 12 weeks of treatment. This was used to assess percent change in GLI1 mRNA levels as follows: (Baseline - Week 12) / Baseline \* 100, with positive numbers to represent increases and negative numbers to represent decreases. Any missing values were not imputed; all available data is summarized.

SEBs were defined as clinically diagnosed BCC 5 to 20 mm in diameter on the face, excluding the nose and periorbital skin, and 9 to 20 mm at sites other than the face. The percent change in greatest diameters of treatment-targeted surgically eligible basal cell carcinomas (SEBs) from Baseline to Week 12 was calculated as follows: (sum \[Baseline\] - sum \[Week 12\] / sum \[Baseline\] \* 100), where sum = the greatest diameters of treatment-targeted SEBs and positive numbers to represent increases and negative numbers to represent decreases. Missing values were imputed using Last-Observation Carried Forward (LOCF).

SEBs were defined as clinically diagnosed BCC 5 to 20 mm in diameter on the face, excluding the nose and periorbital skin, and 9 to 20 mm at sites other than the face. The percentage of tumors showing a complete or partial response at Week 12 was calculated as follows: (Number of baseline treatment-targeted SEBs showing complete or partial response at Week 12) / (Number of Baseline treatment-targeted SEBs) \* 100. Missing values were not imputed.Complete Response is determined when there is no longer any visible evidence of a lesion consistent with BCC at the site, and Partial Response is determined when although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline.

PellePharm, Inc.

All enrolled participants who were randomized, received at least 1 confirmed dose of study drug, and had at least 1 post-baseline safety assessment.

Applied topically once daily for 12 weeks (Cohort 1)

Patidegib Gel 2% - Once Daily

Applied topically once daily for 12 weeks (Cohort 2)

Patidegib Gel 4% - Once Daily

Applied topically twice daily for 12 weeks (Cohort 3)

Patidegib Gel 2% - Twice Daily

Applied topically twice daily for 12 weeks (Cohort 4)

Patidegib Gel 4% - Twice Daily

Applied topically once or twice daily for 12 weeks (Cohorts 1, 2, 3, and 4)

Vehicle Gel

Age, Continuous

Race (NIH/OMB)

Weight

Participants who received at least 1 dose of study drug

Chief Medical Officer

Number of Treatment-emergent Adverse Events (Including Both Serious and Non-Serious) Causally Related to Study Drug

This is the analysis of combined patidegib gel 2% once daily and twice daily compared with vehicle gel at Week 12.

This is the analysis of combined patidegib gel 4% once daily and twice daily compared with vehicle gel at Week 12.

This is the analysis of all four patidegib gel treatment groups combined compared with vehicle gel at Week 12.

Participants who received at least 1 dose of study drug who had evaluable GLI1 mRNA data at Baseline and Week 12.

Molecular Efficacy: Percent Change From Baseline in the Hedgehog (HH) Signaling Pathway Target Gene Glioma-associated Oncogene Homolog 1 (GLI1) Messenger Ribonucleic Acid (mRNA) Levels at Week 12

Patidegib Gel 2% - Cohort 1

Vehicle Gel - Cohort 1

Patidegib Gel 4% - Cohort 2

Vehicle Gel - Cohort 2

Patidegib Gel 2% - Cohort 3

Vehicle Gel - Cohort 3

Patidegib Gel 4% - Cohort 4

Vehicle Gel - Cohort 4

Participants who received at least 1 dose of study drug.

Clinical Efficacy: Percent Change From Baseline in Tumor Size of Treatment-targeted SEBs at Week 12

Clinical Efficacy: Percentage of SEBs Showing Complete or Partial Response at Week 12 as Determined by Blinded Photographic Review

Week 2

Week 6

Week 8

Week 10

Week 12

Percentage of Treatment-targeted SEBs Achieving Clear or Almost Clear on the Investigator Static Global Tumor Assessment (ISGTA) Scale

Percent Change in Treatment-targeted SEBs Tumor Size From Baseline as Determined by Blinded Photographic Review

This is the analysis of all four patidegib gel treatment groups combined compared with combined vehicle gel at Week 12.

The ISGTA is a scale with scores ranging from 0 (clear), 1 (almost clear), 2 (minimal residual tumor), to 3 (clearly visible tumor). The Investigator assessed each Baseline treatment-targeted SEB at Week 12. SEBs were defined as clinically diagnosed BCC 5 to 20 mm in diameter on the face, excluding the nose and periorbital skin, and 9 to 20 mm at sites other than the face. The percentage of Baseline treatment-targeted SEBs evaluated as being clear at Week 12 based on the ISGTA scale and BCC not present was calculated as follows: (Number of baseline treatment-targeted SEBs with ISGTA score of 0 and BCC not present at Week 12) / (Number of Baseline treatment-targeted SEBs) \* 100.

Vehicle gel, applied topically once or twice daily for 12 weeks (Cohorts 1, 2, 3, and 4)

Vehicle Gel - All Cohorts

Percentage of Treatment-targeted SEBs Achieving Clear on the ISGTA Scale and BCC Not Present at Week 12

Carcinoma, Squamous Cell

Keratosis, Actinic

Keratosis

Skin biopsies will be performed according to standard practices in the usual aseptic conditions, the operator wearing sterile gloves. A circular knife 3 mm will be used. Procedure interventions do not involve a drug or a device.

biopsy

Marie BEYLOT-BARRY, MD, PhD

Léa DOUSSET, MD

Christine ALFARO

Skin carcinomas are the most frequent cancers in the world, including basal cell carcinomas and cutaneous squamous cell carcinoma (cSCCs), with more than 60.000 new annual cases in France. Their incidence increases mainly due to ultraviolet (UV) exposure and population ageing. Then from 1994 to 2006, the incidence of cSCC has increased by 300%. CSCCs typically manifests as a spectrum from a precursor actinic keratosis (AK) - possible spontaneous regression at this stage- to in situ cSCC invasive cSCC and finally metastatic cSCC.

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation and how it influences further the bioenergetic behavior of tumors.

By applying a quantitative proteomic approach, the consortium has recently found that specific metabolic modifications precede cSCC.

This study will investigate the role of energy metabolism in malignant transformation of premalignant skin lesions into cSCC, and in cSCC progression, with correlation with clinical characteristics and metastatic outcomes. Using several cutting-edge technologies in human samples, the team will evaluate whether targeting energy metabolism has the potential to be used as curative treatments for cSCC and whether pre-determined metabolic alterations could be exploited as new preventive strategies. These modifications in energy metabolism could be used as prognostic and diagnostic biomarkers.

Study of Metabolic Changes in the Transformation Malignant Precancerous Skin Lesions

Metabolic profiling of different stages of carcinogenesis: glycolysis, oxidative phosphorylation

% of samples in each category (AK, in situ, ...) that present differentiation features are assessed by immunostaining of loricrin, filaggrin, K10

% of samples expressing aggressive markers will be assessed by evaluating the proliferation index, degree of differentiation, invasion beyond subcutaneous fat, perineural invasion, vascular invasion level of infiltration following immunohistochemistry analyses on formalin-fixed paraffin-embedded tissue sections.

% of samples with high apoptotic cell death level will be assessed by immunostaining using antibody against cleaved caspase-3.

% of samples with high mitochondrial activity will be evaluated by comparing oxygen consumption rate by different fresh samples.

% of samples that are highly proliferative will be calculated by measuring the ability of colony formation (SRB Test) and cell cycle progression (flow cytometer, western).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Development of a Nanosecond Pulsed Electric Field System to Treat Skin Cancer	NCT01463709	Basal Cell Carc...	PulseCure pulse...	18 Years - 75 Years	UCSF Benioff Children's Hospital Oakland
Vismodegib in Basal Cell Carcinomas (BCC) Chemoprevention	NCT02067104	Basal Cell Carc...	Vismodegib Placebo	18 Years -	University of Arizona
Treatment of Basal Cell Carcinomas With Methyl Aminolevulinate and Daylight	NCT01349361	Photodynamic Th... Basal Cell Carc...	Daylight mediat...	18 Years -	Bispebjerg Hospital
Vismodegib in Basal Cell Carcinomas (BCC) Chemoprevention	NCT02067104	Basal Cell Carc...	Vismodegib Placebo	18 Years -	University of Arizona
Vismodegib in Basal Cell Carcinomas (BCC) Chemoprevention	NCT02067104	Basal Cell Carc...	Vismodegib Placebo	18 Years -	University of Arizona
Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle Applied Once or Twice Daily to Decrease the GLI1 Biomarker in Sporadic Nodular Basal Cell Carcinomas	NCT02828111	Basal Cell Carc...	Patidegib Vehicle gel	18 Years - 85 Years	PellePharm, Inc.
Study of Metabolic Changes in the Transformation Malignant Precancerous Skin Lesions	NCT04389112	Cutaneous Squam... Basal Cell Carc...	biopsy	18 Years -	University Hospital, Bordeaux
Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle Applied Once or Twice Daily to Decrease the GLI1 Biomarker in Sporadic Nodular Basal Cell Carcinomas	NCT02828111	Basal Cell Carc...	Patidegib Vehicle gel	18 Years - 85 Years	PellePharm, Inc.
Vismodegib in Basal Cell Carcinomas (BCC) Chemoprevention	NCT02067104	Basal Cell Carc...	Vismodegib Placebo	18 Years -	University of Arizona

Spots Global Cancer Trial Database for basal cell carcinomas