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Study of ASN-002 to Treat Basal Cell Carcinomas (BCCs) in Individuals With Basal Cell Nevus Syndrome (BCNS)

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ClinicalTrials.gov Identifier: NCT03208296
Recruitment Status : Suspended (Study did not start. Another protocol is being developed.)
First Posted : July 5, 2017
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
Ascend Biopharmaceuticals Ltd

Brief Summary:

The primary objective is to confirm the safety of treating multiple BCCs once weekly x 3 weeks in individuals with Basal Cell Nevus Syndrome (BCNS).

The secondary objectives of the study are to obtain preliminary data on the effectiveness of ASN-002 in the treatment of BCCs in individuals with Basal Cell Nevus Syndrome (BCNS) by

  1. evaluating the histological clearance of BCCs in patients with BCNS, and
  2. assessing the clinical changes of BCCs after treatment with ASN-002, and
  3. assessing the systemic effect of ASN-002 by determining response in non-injected lesions
  4. assess the safety and clinical changes after a second cycle of ASN-002 injections

Condition or disease Intervention/treatment Phase
Basal Cell Carcinoma in Basal Cell Nevus Syndrome Biological: ASN-002 Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This is a dose escalation study to determine the safety and efficacy of ASN-002 in treatment of BCCs in BCNS patients.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Study of ASN-002 to Treat Basal Cell Carcinomas (BCCs) in Individuals With Basal Cell Nevus Syndrome (BCNS)
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : March 31, 2020


Arm Intervention/treatment
Experimental: Cohort A
Subjects with 4 or more lesions will receive 1.0 x 10^11 vp/injection of ASN-002 into each of 4 BCCs, weekly x 3, i.e. weeks 1, 2, and 3
Biological: ASN-002
ASN-002 has been designed for clinical applications, especially for intratumoral administration in the treatment of various cancers. This rAd vector delivers the gene of interest, in the case of ASN-002 the human IFNγ gene, into target cells. The rAd vector in ASN-002 is replication deficient and although it infects cells, it is not able to replicate in the tumor or in normal human cells. The infected cells are able to transcribe and translate the IFNγ DNA leading to a sustained local concentration of IFNγ in the tumor mass that is designed to avoid high levels of systemic IFNγ that may be lead to unacceptable toxicity.

Experimental: Cohort B 1.5
Subjects with 4 or more lesions will receive 1.5 x 10^11 vp/injection of ASN-002 into each of 3 BCCs, weekly x 3, i.e. weeks 1, 2, and 3
Biological: ASN-002
ASN-002 has been designed for clinical applications, especially for intratumoral administration in the treatment of various cancers. This rAd vector delivers the gene of interest, in the case of ASN-002 the human IFNγ gene, into target cells. The rAd vector in ASN-002 is replication deficient and although it infects cells, it is not able to replicate in the tumor or in normal human cells. The infected cells are able to transcribe and translate the IFNγ DNA leading to a sustained local concentration of IFNγ in the tumor mass that is designed to avoid high levels of systemic IFNγ that may be lead to unacceptable toxicity.

Experimental: Cohort B 1.0
Subjects with 4 or more lesions will receive 1.0 x 10^11 vp/injection of ASN-002 into each of 3 BCCs, weekly x 3, i.e. weeks 1, 2, and 3
Biological: ASN-002
ASN-002 has been designed for clinical applications, especially for intratumoral administration in the treatment of various cancers. This rAd vector delivers the gene of interest, in the case of ASN-002 the human IFNγ gene, into target cells. The rAd vector in ASN-002 is replication deficient and although it infects cells, it is not able to replicate in the tumor or in normal human cells. The infected cells are able to transcribe and translate the IFNγ DNA leading to a sustained local concentration of IFNγ in the tumor mass that is designed to avoid high levels of systemic IFNγ that may be lead to unacceptable toxicity.




Primary Outcome Measures :
  1. Safety of ASN-002 will be studied in terms of AEs reported in individuals with Basal Cell Nevus Syndrome (BCNS) receiving ASN-002 using CTCAE 4.03. [ Time Frame: The assessment will be conducted at every visit after first dose, week1, week2, week 3, Months1, 2, 3, 4 and at Month 6. ]
    Clinical safety will assessed in terms of changes in vital signs, AEs, serious AEs (SAEs), 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 using protocol-specific modifications of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03.


Secondary Outcome Measures :
  1. Treatment efficacy in term of percentage of histological cure of BCC lesions at 6 months [ Time Frame: 6 months from baseline ]
    At the end of the study, BCC lesions will be excised and studied under microscope to study the complete cure of BCC i.e. histological clearance

  2. Clinical changes in BCCs after treatment with ASN-002 in- terms of change in lesion size (mm) [ Time Frame: 6 months from baseline. ]
    The BCC lesions will be measured in mm at baseline, after first dose at Months1, 2, 3, 4 and at Month 6 to study the change in lesion size and clinical response.

  3. The systemic effect of ASN-002 will be assessed for non-injected lesions by studying the change in lesion size from baseline to end of the study. [ Time Frame: 6 months from baseline ]
    The non-injected BCC lesions will be measured in mm at baseline, after first dose at Months1, 2, 3, 4 and at Month 6 to study the change in lesion size and clinical response.

  4. The safety in terms of the AEs reported (using CTCAE 4.03) after 6 months from first dose in retreatment cycle [ Time Frame: 6 months ]
    Clinical safety will assessed in terms of changes in vital signs, AEs, serious AEs (SAEs), 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 using protocol-specific modifications of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

  5. The systemic effect of ASN-002 will be assessed for non-injected lesions by studying the rate of histological clearance after 6 months of first dose. [ Time Frame: 6 months from baseline ]
    At the end of the study, BCC lesions will be excised and studied under microscope to study the complete cure of BCC i.e. histological clearance

  6. The efficacy will be assessed in terms of change in lesion size (mm) after 6 months from first dose in retreatment cycle [ Time Frame: 6 months ]
    The change in lesions size in mm will be studied after 6 months from first dose in retreatment cycle.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Must satisfy established criteria for the diagnosis of BCNS (Section 1.1.2, Table 1).
  2. Must have at least 4 target lesions, clinically consistent with BCC.
  3. Up to 6 target lesions, including each of the 3 or 4 to-be-injected lesions and 1 or 2 non-injected lesions must be biopsied.
  4. At least 3 target lesions, 2 to be injected and one to be non-injected, must be biopsy proven BCC per criteria in Synopsis Table 3: Modified Criteria for Low Risk BCC in BCNS Patients
  5. Removal of < 25% of the area of the tumor by initial biopsy performed within 12 weeks before screening visit. A 2mm punch biopsy is recommended for histological confirmation of BCC.
  6. Screening laboratory values as follows:

    1. Neutrophil count > 1500/mm3
    2. Hemoglobin > 10 g/dL
    3. Platelet count > 100,000/mm3
    4. Total bilirubin < 1.5 X upper limit of normal (ULN), except in the case of known Gilbert's syndrome
    5. Aspartate transaminase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) < 1.5X ULN
    6. Creatinine < 1.5 X upper limit of normal (ULN)
  7. 18 years of age or older at Screening visit.
  8. Infertile, postmenopausal, surgically sterile or using acceptable and highly effective birth control methods for the duration of the study and for 3 months after last administration of ASN-002.
  9. Written informed consent prior to initiation of study-specified procedures.
  10. Able and willing to comply with all study requirements, including surgical removal of tumor/tumor sites as required by the study.

Exclusion Criteria:

  1. Target tumor biopsy shows evidence of:

    • micronodular features,
    • squamous metaplasia,
    • sclerosing BCC,
    • morpheic BCC, or
    • peri-neural involvement.
    • cystic BCC
  2. Eastern Cooperative Oncology Group (ECOG) performance status > 2.
  3. Known or suspected metastatic disease.
  4. Female participants must be non-lactating and non-pregnant.
  5. Clinically active or uncontrolled skin disease that would interfere with evaluation of the area surrounding the target tumor (e.g. eczema, unstable psoriasis, xeroderma pigmentosa).
  6. Known history of sensitivity to any of the ingredients in ASN-002.
  7. Immunocompromised (e.g. known hepatitis B or C or HIV infection) or is receiving or is expected to receive an immunomodulating agent (including immunosuppressive agents, cytotoxic drugs, biological agents, immunoglobulins, interferon or other immune or cytokine-based therapies; regular use of inhaled or oral corticosteroids at doses higher than replacement doses is an exclusion criterion).
  8. Treatment with psoralen plus UVA or UVB therapy within 3 months of screening and agrees not to receive such treatment until excision site is confirmed to be well healed at the post-surgery study visits
  9. Prior systemic or local treatment for target tumors.
  10. History of immunological disorder, severe allergic reaction, moderate or severe asthma or known history of anaphylaxis or any other serious adverse reactions to any medication.
  11. Any serious or active medical or psychiatric illness or recreational or therapeutic drug or alcohol use that, in the opinion of the Investigator, would interfere with treatment, assessment or compliance with the protocol, or subject safety.
  12. Any experimental or investigational agents within 1 month of first injection.
  13. Any prior exposure to TG1041, TG1042 (ASN-002), any other adenoviral-based experimental agent within 5 months prior to screening visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03208296


Locations
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United States, Oregon
OHSU
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Ascend Biopharmaceuticals Ltd
Investigators
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Study Chair: Clement Leong Ascend Biopharmaceuticals Ltd
Principal Investigator: Anna Bar Oregon Health and Science University

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Responsible Party: Ascend Biopharmaceuticals Ltd
ClinicalTrials.gov Identifier: NCT03208296     History of Changes
Other Study ID Numbers: ASN-002-002
First Posted: July 5, 2017    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: The decision will be taken in due course of time.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ascend Biopharmaceuticals Ltd:
Basal Cell Nevus Syndrome
Basal Cell Carcinoma

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Basal Cell
Nevus
Basal Cell Nevus Syndrome
Nevus, Pigmented
Syndrome
Disease
Pathologic Processes
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Basal Cell
Nevi and Melanomas
Odontogenic Cysts
Jaw Cysts
Bone Cysts
Cysts
Neoplastic Syndromes, Hereditary
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Jaw Diseases
Stomatognathic Diseases
Abnormalities, Multiple
Congenital Abnormalities
Genetic Diseases, Inborn