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Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor

Primary Purpose

Basal Cell Carcinoma, Basal Cell Nevus Syndrome

Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
ASN-002
Sponsored by
Ascend Biopharmaceuticals Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Basal Cell Carcinoma focused on measuring high frequency basal cell carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically confirmed previously untreated, BCC (nodular and superficial), 5-20 mm in maximum diameter, per the selection criteria for study BCC tumours. A punch biopsy (refer to study procedure manual for biopsy size selection) from the thickest part of all the target tumours is required for histological confirmation of BCC and to exclude BCC non-eligible subtypes.

    Note: If a patient has mix of nodular and superficial BCC tumours, at least one target tumour should be a nodular BCC.

  2. Removal of < 25% of the area of each biopsied tumour by initial biopsy performed 1-12 weeks before Day 1. If the initial biopsy was performed >8 weeks prior to screening, the investigator may re-biopsy the tumour, provided not > 25% of the area of the original tumour is removed. Non-study tumours may be resected or treated at the discretion of the Investigator prior to study entry or if they develop during the study.
  3. Hedgehog pathway inhibitor treatment naïve.
  4. Acceptable general health as determined by the investigator, i.e. no 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, ability to provide informed consent, or patient safety.
  5. 18 years of age or older.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
  7. Screening laboratory values as follows:

    1. Neutrophil count > 1500/mm3
    2. Haemoglobin > 9 g/dL
    3. Platelet count >100,000/mm3
    4. Prothrombin INR < 1.5
    5. Total bilirubin < 1.5 X upper limit of normal (ULN), except in the case of known Gilbert's syndrome
    6. Aspartate transaminase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) < 2X ULN
    7. Creatinine < 1.5 X upper limit of normal (ULN)
  8. Female patients who are documented infertile, postmenopausal for at least 1 year, surgically sterile or using acceptable and highly effective birth control for the duration of the study and for at least 3 months after last administration of the study treatments.
  9. Male patients with female partners of child bearing potential, agreement to use two adequate contraception methods while being on vismodegib and for 3 months of completion. agreement not to donate semen for 3 months after completion of vismodegib.
  10. Written informed consent prior to initiation of study-specified procedures.
  11. Able and willing to comply with all study requirements, including surgical removal of tumour/tumour site at completion of study.
  12. Baseline tissue sample adequate for determination of histological or other biomarkers.

Exclusion Criteria

  1. Known or suspected metastatic disease or other active, invasive malignancy.
  2. Female patients of childbearing potential who are lactating or pregnant (negative serum pregnancy test needed prior to dosing).
  3. Clinically active or uncontrolled skin disease or tattoos that would interfere with evaluation of the area surrounding the target tumour (e.g. eczema, unstable psoriasis, xeroderma pigmentosa).
  4. Known history of sensitivity to any of the ingredients in ASN-002 and any Hh pathway inhibitors.
  5. Immunocompromised (e.g. known Hepatitis B or C infection, HIV infection) or receiving or expected to receive an immunomodulating agent (including immunosuppressive agents, cytotoxic drugs, biological agents, immunoglobulins, interferon or other immune or cytokine-based therapies. Use of inhaled or oral corticosteroids at doses higher than physiological replacement doses is an exclusion criterion).
  6. Has received or is expected to receive treatment with psoralen plus UVA or UVB therapy within 6 months of the Screening visit.
  7. Any prior systemic anti-tumour therapy or local treatment for target tumours prior to first dose.
  8. 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.
  9. Any experimental or investigational agents within one month of first ASN-002 injection.
  10. Any prior exposure to TG1041, TG1042 (ASN-002), any other adenoviral-based experimental agent, or any form of gene therapy within 6 months of first dose of vismodegib in the study.
  11. Any prior exposure to vismodegib or any other Hh inhibitor within 6 months of first dose in the study.
  12. Current therapy with any medications recognized to cause rhabdomyolysis or a prior history of rhabdomyolysis.

Sites / Locations

  • Central Brisbane DermatologyRecruiting
  • Princess Alexandra Hospital
  • Veracity Clinical Research
  • Sunshine Coast University Hospital
  • Sinclair Dermatology
  • Royal Melbourne HospitalRecruiting
  • Burswood DermatologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1, Patients with 1 Tumour

Arm 2, Patients with 3 or more Tumours

Arm Description

Participants with 1 Target Tumour will receive 3 x ASN-002 1.0x10(11) Injections + VISMODEGIB (150 mg) daily for 4 weeks.

Participants with 3 or more Target Tumours will receive 3 x ASN-002 1.0x10(11) Injections (per tumour) + VISMODEGIB (150 mg) daily for 4 weeks.

Outcomes

Primary Outcome Measures

Incidence of ASN-002 related Adverse Events in patients with previously untreated nBCC
Incidence of Adverse Adverse events will be monitored
Microscopic clearance of the injected Target 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.

Secondary Outcome Measures

Microscopic clearance of the injected Non-Target 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.

Full Information

First Posted
May 21, 2020
Last Updated
December 14, 2022
Sponsor
Ascend Biopharmaceuticals Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT04416516
Brief Title
Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor
Official Title
A Phase 2A Study to Assess the Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor in the Treatment of Multiple Low Risk Basal Cell Carcinomas in Sporadic or Basal Cell Nevus Syndrome Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 16, 2020 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascend Biopharmaceuticals Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objectives are to: Evaluate the safety and tolerability of intralesional ASN-002 when administered in combination with oral vismodegib in patients with Basal Cell Carcinomas (BCC)s; Evaluate the efficacy of intralesional ASN-002 in target tumours when administered in combination with oral vismodegib in patients with BCCs. The secondary objective is to: 1) Evaluate the efficacy of intralesional ASN-002 in non-target tumours when administered in combination with oral vismodegib in patients with BCCs. The exploratory objective is to: 1) Evaluate immunological biomarkers during the course of treatment.
Detailed Description
Methodology: This study will evaluate ASN-002 (in the dose range 0.5 to 1.5x10(11) vp/mL) with the Hh inhibitor vismodegib (Erivedge®). The study will initially evaluate two Arms receiving 1.0 x 10(11) vp/injection, and following a safety review, may implement further arms in an adaptive study design. Following screening and baseline biopsies for target and non-target tumours, eligible subjects will be enrolled in the study. Cycle 1: Treatment with vismodegib (daily dose of 150 mg) for 4 weeks and ASN-002 for 3 weeks (i.e., three ASN-002 injections in total): Day 1 to Day 14 - vismodegib alone Day 15 - vismodegib and ASN-002 Day 16 to Day 21 - vismodegib alone Day 22 - vismodegib and ASN-002 Day 23 to Day 28 - vismodegib alone Day 29 - ASN-002 alone Clinical response will be assessed at Week 17, following which, the investigator may where clinically indicated, initiate Cycle 2. Cycle 2: Treatment with vismodegib (daily dose of 150 mg) for 4 weeks, and one further injection with ASN-002: Day 1 to Day 7 - vismodegib alone Day 8 - vismodegib and ASN-002 Day 9 to Day 28 - vismodegib alone Surgical excision for all patients will occur between Week 25 and Week 33 at the investigators discretion, and dependent on when patient completed study treatment (1 or 2 treatment cycles). Up to 10 BCCs to be excised including 3 target tumours. Excisions can be conducted over 2 visits as per Investigator's discretion. The Investigator may enrol eligible patients parallel into either Arm 1 or Arm 2, based on the number of tumours present. Up to 10 study BCC tumours (up to 3 target and up to 7 non-target) will be selected per patient. Following review of at least Week 5 data for N=6 patients in Arm 1 and Arm 2, further Arms with varying doses of ASN-002 (in the dose range 0.5x10(11) vp or 1.5x10(11) vp) may be explored at the discretion of the Safety Review Committee (SRC). Vismodegib or ASN-002 may be evaluated as monotherapies to provide control groups to allow comparison of treatment Arms. Safety and clinical assessments will be performed at Weeks 1, 3, 4, 5, 7, 17, 25 to 33. Histological response will be evaluated in all study tumours via excision between Week 25 and Week 33 (as per investigator's discretion). Six patients will be recruited to each Arm of the study, each Arm may be expanded to 12 patients at the discretion of the SRC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Basal Cell Carcinoma, Basal Cell Nevus Syndrome
Keywords
high frequency basal cell carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1, Patients with 1 Tumour
Arm Type
Experimental
Arm Description
Participants with 1 Target Tumour will receive 3 x ASN-002 1.0x10(11) Injections + VISMODEGIB (150 mg) daily for 4 weeks.
Arm Title
Arm 2, Patients with 3 or more Tumours
Arm Type
Experimental
Arm Description
Participants with 3 or more Target Tumours will receive 3 x ASN-002 1.0x10(11) Injections (per tumour) + VISMODEGIB (150 mg) daily for 4 weeks.
Intervention Type
Biological
Intervention Name(s)
ASN-002
Intervention Description
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 Measure Information:
Title
Incidence of ASN-002 related Adverse Events in patients with previously untreated nBCC
Description
Incidence of Adverse Adverse events will be monitored
Time Frame
Participants will be followed up to 6 months
Title
Microscopic clearance of the injected Target basal cell carcinoma.
Description
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.
Time Frame
Microscopic examinations of sample collected at weeks 25-33 after the first dose.
Secondary Outcome Measure Information:
Title
Microscopic clearance of the injected Non-Target basal cell carcinoma.
Description
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.
Time Frame
Microscopic examinations of sample collected at weeks 25-33 after the first dose.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed previously untreated, BCC (nodular and superficial), 5-20 mm in maximum diameter, per the selection criteria for study BCC tumours. A punch biopsy (refer to study procedure manual for biopsy size selection) from the thickest part of all the target tumours is required for histological confirmation of BCC and to exclude BCC non-eligible subtypes. Note: If a patient has mix of nodular and superficial BCC tumours, at least one target tumour should be a nodular BCC. Removal of < 25% of the area of each biopsied tumour by initial biopsy performed 1-12 weeks before Day 1. If the initial biopsy was performed >8 weeks prior to screening, the investigator may re-biopsy the tumour, provided not > 25% of the area of the original tumour is removed. Non-study tumours may be resected or treated at the discretion of the Investigator prior to study entry or if they develop during the study. Hedgehog pathway inhibitor treatment naïve. Acceptable general health as determined by the investigator, i.e. no 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, ability to provide informed consent, or patient safety. 18 years of age or older. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. Screening laboratory values as follows: Neutrophil count > 1500/mm3 Haemoglobin > 9 g/dL Platelet count >100,000/mm3 Prothrombin INR < 1.5 Total bilirubin < 1.5 X upper limit of normal (ULN), except in the case of known Gilbert's syndrome Aspartate transaminase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) < 2X ULN Creatinine < 1.5 X upper limit of normal (ULN) Female patients who are documented infertile, postmenopausal for at least 1 year, surgically sterile or using acceptable and highly effective birth control for the duration of the study and for at least 3 months after last administration of the study treatments. Male patients with female partners of child bearing potential, agreement to use two adequate contraception methods while being on vismodegib and for 3 months of completion. agreement not to donate semen for 3 months after completion of vismodegib. Written informed consent prior to initiation of study-specified procedures. Able and willing to comply with all study requirements, including surgical removal of tumour/tumour site at completion of study. Baseline tissue sample adequate for determination of histological or other biomarkers. Exclusion Criteria Known or suspected metastatic disease or other active, invasive malignancy. Female patients of childbearing potential who are lactating or pregnant (negative serum pregnancy test needed prior to dosing). Clinically active or uncontrolled skin disease or tattoos that would interfere with evaluation of the area surrounding the target tumour (e.g. eczema, unstable psoriasis, xeroderma pigmentosa). Known history of sensitivity to any of the ingredients in ASN-002 and any Hh pathway inhibitors. Immunocompromised (e.g. known Hepatitis B or C infection, HIV infection) or receiving or expected to receive an immunomodulating agent (including immunosuppressive agents, cytotoxic drugs, biological agents, immunoglobulins, interferon or other immune or cytokine-based therapies. Use of inhaled or oral corticosteroids at doses higher than physiological replacement doses is an exclusion criterion). Has received or is expected to receive treatment with psoralen plus UVA or UVB therapy within 6 months of the Screening visit. Any prior systemic anti-tumour therapy or local treatment for target tumours prior to first dose. 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. Any experimental or investigational agents within one month of first ASN-002 injection. Any prior exposure to TG1041, TG1042 (ASN-002), any other adenoviral-based experimental agent, or any form of gene therapy within 6 months of first dose of vismodegib in the study. Any prior exposure to vismodegib or any other Hh inhibitor within 6 months of first dose in the study. Current therapy with any medications recognized to cause rhabdomyolysis or a prior history of rhabdomyolysis.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clement Leong, Ph.D
Phone
+61 421 837 218
Email
clementleong@ascendbiopharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Cleo Moore
Phone
+64 488 942 145
Email
cleomoore@ascendbiopharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clement Leong, Ph.D
Organizational Affiliation
Ascend Biopharmaceuticals Ltd
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Gregory Siller
Organizational Affiliation
Central Brisbane Dermatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Central Brisbane Dermatology
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gregory M Siller, MBBS, ECFMG, FACD
Phone
(07) 3831 4382
Email
research@cbdermatology.com.au
First Name & Middle Initial & Last Name & Degree
Thomas M Pitney, MBBS
Phone
(07) 3831 4382
Email
research@cbdermatology.com.au
Facility Name
Princess Alexandra Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kiarash Khosrotehrani, MD PhD FACD
Email
k.khosrotehrani@uq.edu.au
Facility Name
Veracity Clinical Research
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Completed
Facility Name
Sunshine Coast University Hospital
City
Sunshine Coast
State/Province
Queensland
Country
Australia
Individual Site Status
Completed
Facility Name
Sinclair Dermatology
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Individual Site Status
Completed
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sonia Maleki
Phone
+ 61 3 9342 4542
Email
sonia.maleki@mh.org.au
Facility Name
Burswood Dermatology
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6100
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pamela Clements
Phone
+6189470 3064
Email
pamyclements@hotmail.com

12. IPD Sharing Statement

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Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor

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