The primary objectives are to: 1. Evaluate the safety and tolerability of intralesional ASN-002 when administered in combination with oral vismodegib in patients with Basal Cell Carcinomas (BCC)s; 2. 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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
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.
Central Brisbane Dermatology
Brisbane, Queensland, Australia
Princess Alexandra Hospital
Brisbane, Queensland, Australia
Veracity Clinical Research
Brisbane, Queensland, Australia
Sunshine Coast University Hospital
Sunshine Coast, Queensland, Australia
Sinclair Dermatology
Melbourne, Victoria, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia
Burswood Dermatology
Perth, Western Australia, Australia
Incidence of ASN-002 related Adverse Events in patients with previously untreated nBCC
Incidence of Adverse Adverse events will be monitored
Time frame: Participants will be followed up to 6 months
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.
Time frame: Microscopic examinations of sample collected at weeks 25-33 after the first dose.
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.
Time frame: Microscopic examinations of sample collected at weeks 25-33 after the first dose.
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