A Study of the Efficacy and Safety of ASN-002 in Adult Patients With Low-risk Nodular Basal Cell Carcinoma

Study Overview
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Brief Summary
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The study evaluates whether ASN-002 is safe and effective in the treatment of nodular basal cell carcinoma (nBCC) in patients aged 18 years or over. The participants will receive weekly injections of ASN-002 alone or in combination with 5-FU for 3 weeks and undergo surgical excision of the tumor.

Detailed Description
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The primary purpose of this study is to determine whether ASN-002 alone or in combination with 5-FU is safe and effective in the treatment of nodular basal cell carcinoma (nBCC). Patients aged 18 or over, who have been diagnosed with nodular Basal Cell Carcinoma (nBCC), may be eligible to join this study. Study details: ASN-002 is an immunotherapeutic product that is injected into the BCC spot to be treated. It is made from modified adenovirus serotype 5 (also called Ad5). Adenoviruses are common in nature worldwide and can cause mild colds and respiratory infections from which people usually recover without treatment. The Ad5 used in this study has been modified so that it cannot grow in the body or cause an infection. The modified Ad5 in this study will deliver artificially made genetic material into the cancerous and surrounding cells. This genetic material will produce human interferon which is normally produced by the body to stimulate the immune system. It is hoped that injected ASN-002 will cause the body's own cells to produce interferon and stimulate the immune system to attack the cancerous cells and reduce the size of or eliminate the nBCC. Participants will attend the study centre weekly for an injection of ASN-002 alone of in combination with 5-FU into the nBCC. The participants recruited will have 3 injections over 3 weeks, and then undergo surgical excision of the tumor. Patient outcomes will then be assessed using a tumour sample collected during surgery and by the incidence of adverse events which occur throughout the study. It is hoped that the findings of this trial will provide information on the safety and efficacy of using ASN-002 alone or in combination with 5-FU for nBCC, particularly for patients in whom the standard treatment of surgery is not possible or not recommended.

Official Title
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A Phase 1/2a Study of the Efficacy and Safety of ASN-002 Alone or in Combination With 5-FU in Adult Patients With Low-risk Nodular Basal Cell Carcinoma

Conditions
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Basal Cell Nevus Syndrome, Skin Neoplasm, Nodular Basal Cell Carcinoma of Skin

Intervention / Treatment
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* Biological: ASN-002
* Drug: 5-FU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Low risk nodular basal cell carcinoma Biopsy of any other skin tumor Willingness to have injection therapy followed by surgery Written informed consent Exclusion Criteria: No or only minimal symptoms Known or suspected metastatic disease. Pregnant or Lactating females Clinically active or uncontrolled skin disease Immunocompromised or receiving immunomodulating agent treatment with psoralen plus Ultraviolet A or Ultraviolet B light therapy within 6 months Any serious or active medical or psychiatric illness Recreational or therapeutic drug or alcohol use Taking any investigational product within 1 month of first dose of ASN- 002.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Study Participants will receive ASN-002 at a dose 5X 10(10) vp, weekly injection in tumor nodules for 3 weeks. | Biological: ASN-002<br>* ASN-002, is made of a suspension of recombinant adenoviral particles carrying a gene coding for the human interferon-gamma (IFN). Study participants will receive protocol defined dose of ASN-002 as intra-tumoral injections.<br>|
| Experimental: Cohort 2<br>Study Participants will receive ASN-002 at a dose of 1.5X 10(11) vp weekly injection in tumor nodules for 3 weeks | Biological: ASN-002<br>* ASN-002, is made of a suspension of recombinant adenoviral particles carrying a gene coding for the human interferon-gamma (IFN). Study participants will receive protocol defined dose of ASN-002 as intra-tumoral injections.<br>|
| Experimental: Cohort 4<br>Study Participants will receive ASN- 002 at a dose of 3.0X 10(11) vp weekly injections in tumor nodules for 3 weeks. | Biological: ASN-002<br>* ASN-002, is made of a suspension of recombinant adenoviral particles carrying a gene coding for the human interferon-gamma (IFN). Study participants will receive protocol defined dose of ASN-002 as intra-tumoral injections.<br>|
| Experimental: Cohort 5<br>Study Participants will receive ASN- 002 at a dose of 2.25X 10(11) vp weekly injections in tumor nodules for 3 weeks. | Biological: ASN-002<br>* ASN-002, is made of a suspension of recombinant adenoviral particles carrying a gene coding for the human interferon-gamma (IFN). Study participants will receive protocol defined dose of ASN-002 as intra-tumoral injections.<br>|
| Experimental: Combination Cohorts<br>Study Participants will receive ASN- 002 at either dose of Cohorts II, IV or V in combination with a low dose 5-FU (1mg/2.5 mg/5mg/10mg or 25mg) weekly injections in tumor nodules for 3 weeks. | Biological: ASN-002<br>* ASN-002, is made of a suspension of recombinant adenoviral particles carrying a gene coding for the human interferon-gamma (IFN). Study participants will receive protocol defined dose of ASN-002 as intra-tumoral injections.<br>Drug: 5-FU<br>* 5-FU is chemotherapeutic agent used to treat various cancers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidences of ASN-002 related Adverse Event in patients with previously untreated nBCC | changes in vital signs, adverse events, serious adverse events, laboratory abnormalities and withdrawals from study. Local skin and injection site reactions will be assessed in detail scoring erythema, ulceration, pain and overall severity as none, mild, moderate or severe. | Participants will be followed up for up to 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microscopic clearance of the injected basal cell carcinoma. | Histological clearance (HC) will be defined as the absence of detectable evidence of BCC tumor cell nests in serial histological samples as determined by central pathology review. | Microscopic examinations of sample collected at 17weeks after the first dose. | 
| Clinical Changes in size of nBCC tumor over time after treatment with ASN-002 alone or in combination with 5-FU | Change in nBCC lesion size will be assessed by investigator at baseline and then every 4 weeks until the surgical excision of BCC after ASN-002 therapy. | Change in nBCC will be assessed for up to 6 months from the first treatment visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Untreated nBCC, Low-Risk