None listed
Conditions
Brief summary
This study will assess the safety and tolerability of a novel photodynamic (light activated) ointment called INV043 in adults with non-melanoma skin cancers. Who is it for? You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with cutaneous squamous cell carcinoma (cSCC) or superficial basal cell carcinoma (BCC) non-melanoma skin cancer. Study details Participants who are eligible for this study will be in enrolled in one of two parts. Participants who are enrolled in Part 1 will have a small dose of INV043 ointment applied to their skin cancer which will then be removed prior to the cancer being exposed to a medical light for up to 750 seconds. Participants will then be asked to return home and report any side effects they experience, including if they don't experience any. Participants who are enrolled into Part 2 will also have a small dose of INV043 ointment applied to their skin cancer which will then be removed prior to the cancer being exposed to a medical light for up to 7,200 seconds. In this study, the specific dose of light exposure will be increased or decreased between groups of participants to determine the optimum light exposure. All participants who enrol in any of these studies will be asked to attend two check up appointments at 6 and 12 months after their light exposure therapy. It is hoped this research will determine the safest and most effective dose of INV043 ointment and medical light therapy that can treat non-melanoma skin cancers.
Interventions
This is a Phase 1, Open Label, First in Human (FIH) Study Investigating Photodynamic Therapy (PDT) with INV043 0.5% Ointment in Adults with Non- melanoma Skin Cancers consisting of 2 parts:
• Part 1: Light dose escalation (fixed Dose Light Interval [DLI])
• Part 2 (optional dose escalation): DLI optimisation
A 3+3 dose escalation design will be utilized to guide light dose escalation in Part 1 according to the table below.
An accelerated titration design will be utilised to guide dose escalat
This is a Phase 1, Open Label, First in Human (FIH) Study Investigating Photodynamic Therapy (PDT) with INV043 0.5% Ointment in Adults with Non- melanoma Skin Cancers consisting of 2 parts: • Part 1: Light dose escalation (fixed Dose Light Interval [DLI]) • Part 2 (optional dose escalation): DLI optimisation A 3+3 dose escalation design will be utilized to guide light dose escalation in Part 1 according to the table below. An accelerated titration design will be utilised to guide dose escalation in Part 2. The design will enrol a minimum of one participant per light dose level until 1 or more participant experiences 2 or more clinically significant, treatment-related > Grade 2 AE, following which dose escalation will follow a 3+3 design, starting with enrolment of a minimum 2 additional participants at that DLI. Study periods will consist of: • Screening Period: Screening period of up to 28 days • Treatment Period: 14 days • Follow-up Period: up to 12 months post-treatment •Treatment with Ointment and Light Source occur on Day 1 of the Protocol schema and only administered once during the course of the study for the patient during both Part 1 and 2. Participants who did not achieve a complete response on the treated lesion following initial treatment with INV043 PDT may undergo a repeat treatment on the same lesion following discussion and approval from study Sponsor. Retreated participants can be enrolled to any Part of the study depending on the part/cohort open at the time and provided the participant meets the retreatment eligibility criteria Combination Investigational products: INV043 Xingda XD660 LAS 1.1 (Photosensitiser) INV043 is formulated as 5 mg per gram ointment, 0.5% w/w ointment for dermal application. Excipients include polyvinylpyrrolidone (PVP, as Kollidon 12 PF, same as povidone), dimethyl sulfoxide (DMSO), polyethylene glycol (PEG) 400 and PEG 1500. INV043 is a phyllochlorin derivative comprising a chlorin molecule linked to a thioglucose moiety designed to facilitate the drug’s localisation into tumour cells. INV043 is a dark blue-green flaky solid. It is essentially insoluble in water. It is soluble in ethanol and DMSO. The ointment is dark blue-green. Container for ointment: INV043 0.5% w/w ointment (2 g) is filled into 2 mL USP Type 1 amber borosilicate glass vials capped with a removable bromobutyl stopper and crimped with a tear-off aluminium vial seal. Dose/amount/volume of ointment per application 2 g (10 mg INV043 equivalent). The weight of INV043 ointment applied will be recorded by weighing the container containing the ointment before and after topical application. INV043 ointment will be rubbed into the lesion and spread 2-3 mm into the surrounding skin. It will be removed with gauze just prior to illumination. Light Source Model: Xingda Laser Model PDT652, manufactured by Xingda Photoelectric Medical Equipment Co Ltd, Guilin, China Wavelength: 660 nm; Intensity: 100 mW/cm2 Light Dose: (J/cm2) will be evaluated. Current timing of the light source is as follows: LD-2**- 36J/cm2 for 6 minutes LD-1**- 50J/cm2 for 8 minutes and 20 seconds LD1 - 75J/cm2 for 12 minutes and 30 seconds LD2 (optional)* - 100j/cm2 for 16 minute and 40 seconds LD3 (optional)* - 125J/cm2 for 20 minutes and 50 seconds (Abbreviations: LD, Light Dose. Notes: *LD2, LD3 and LD4 may be explored if there is insufficient clinical activity observed in LD1. ** If required, lower dose levels will be explored to determine the optimal biological dose in LD-1 and LD-2) Participant Population: Part 1 and Part 2: cutaneous squamous cell carcinoma (cSCC) Other NMSCs may be approved on a case-by-case basis by Sponsor if deemed to be in the participant’s best interest by PI judgment, and unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome. Part 2 (optional): Dose-light interval (DLI) Optimisation An accelerated titration design will be utilised to guide dose escalation in Part 2. The design will enrol a minimum of one participant per light dose level until 1 or more participant experiences 2 or more clinically significant, treatment-related > Grade 2 AE, following which dose escalation will follow a 3+3 design, starting with enrolment of a minimum 2 additional participants at that DLI. The table below summarises the DLIs to be investigated. DLI -2 5 minutes DLI -1 10 minutes DLI 1 30 minutes DLI 2 1 hour DLI 3 2 hours Its Anticipated after each cohort completed the next cohort would commence approx 2- weeks after the conclusion of the previous cohort to allow for review of the Last Patient Last visit and Data safety meeting to occur and data reviewed. The intervention would be provided at Veracity Clinical Research Institute in Australia by a qualified dermatologist (the principal investigator)
Sponsors
Invion Limited
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria 1. Participant is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and is willing and able to return for all study visits and comply with all protocol requirements and procedures. 2. Participant is at least 18 years of age at the time of signing the informed consent. 3. ECOG performance status of 0 or 1. 4. Participants must have a life expectancy of greater then 12 months in the opinion of the Investigator. 5. Participants must have measurable disease based on RECIST 1.1. 6. Participants must have available archival tissue (at least 15 consecutive, unstained, formalin-fixed, paraffin embedded [FFPE] slides or 1 FFPE block) OR, alternatively, a fresh tumour biopsy sample. Participants without any archival tissue or fresh biopsy sample, or who refuse to provide archival tissue may be approved to enrol on a case-by-case basis in discussion with the Sponsor. 7. At least one primary, clinically diagnosed and histologically confirmed, Non-melanoma Skin Cancer lesion. Lesion must meet the following guidelines: • Target lesion must be between 1.0 to 2.0 cm (inclusive) in longest diameter. • Target lesion must be located on a body site easily accessible for topical application by the clinician, excluding the face and scalp area, genitals, perianal area, eyelids, ears. • Target lesion must not be located in areas with significant confounding factors, such as tattoos or deformities, that may put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome. • Participants with lesions that are greater then 2.0 cm and/or lesions located in the face, scalp, genitals, perianal, eyelids or ears, may be allowed on a case-by-case basis in discussion with study Sponsor if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome. 8. For Part 1 and Part 2 (dose escalation cohorts), all participants must meet either of the following tumour-type criteria: a. Non-metastatic cutaneous SCC. b. Other NMSCs may be approved on a case-by-case basis by Sponsor if deemed to be in the participant’s best interest by PI judgment, and unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome. 10. Participants must not require immediate surgical removal of treatment-targeted lesions. Targeted lesion must, in the assessment of the Investigator, be appropriate for study treatment over the anticipated duration of the study. Lesions that otherwise exhibit aggressive features by Investigator judgment should not be included and should be treated with appropriate standard of care. 11. The participant must be willing and able to abstain from using prohibited therapies, including the use of moisturizers or other topical non-medical treatments at the treatment site, for at least 24 hours before INV043 PDT and during study Treatment Period. . 12. Agree to abstain from sun exposure at the treatment site for the duration of the study to End of Treatment Visit (EOTV). 13. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin (ß-hCG) test within 48 hours before the first dose of treatment administration and must not be breastfeeding. 14. WOCBP are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants less then 50 years old who meet the criteria for post-menopausal status without previous surgical sterilisation should be considered for further investigation with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels to confirm serological post-menopausal status. 15. Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive measures from Screening until 14 days after the last dose of study treatment. A female participant must also not be breast feeding and must have a negative pregnancy test (prior to start of dosing and for 14 days after the last dose of study treatment) if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the criteria such as Female participants of childbearing potential are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants <50 years old who meet the criteria for post-menopausal status without previous surgical sterilisation should be considered for further investigation with LH and FSH levels to confirm serological post-menopausal status. 16. Male participants or participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during the study and for 14 days after the last dose of study treatment. All male participants must agree to not donate sperm during the study and for 14 days after the last dose of study treatment. 17. Adequate baseline organ function, as demonstrated by the following: • Serum creatinine less then or equal 2 x institutional ULN • Serum albumin greater then or equal to 2.5 g/dl. • Bilirubin less then or equal to 2.0 x institutional ULN. • AST and ALT less then or equal to3.0 x institutional ULN. 18. Adequate baseline hematologic function, as demonstrated by the following: • ANC greater then or equal to 1.5x109/L. • Haemoglobin greater then or equal to 9 g/dL and no red blood cell (RBC) transfusions during the prior 14 days. • Platelet count greater then or equal to 100x109/L and no platelet transfusions during the prior 14 days.
Exclusion criteria
1. Participants with high-risk cutaneous SCC as per the National Comprehensive Cancer Network (NCCN) guidelines. High risk criteria includes depth of the tumour >2 mm, tumour diameter >2 cm, poor differentiation, perineural invasion, or involvement of the ear or lip mucosa. Additional high-risk factors include immunocompromised participants and fast-growing or recurrent tumours. 2. Participants with morpheaform, metatypical, basosquamous, or infiltrating BCC histologies, if the target lesion is a recurrent BCC. 3. Participants with known metastatic disease from the disease to be studied, e.g., metastatic cutaneous SCC or BCC. 4. Any other known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer. Participants with a history of malignancies of low recurrence potential who have received curative-intent therapy may be approved on a case-by-case basis in discussion with study sponsor, if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome. 5. Use of another investigational product within 60 days, within 5 half-lives, or twice the duration of biological effect, whichever is the longest, prior to INV043 PDT. 6. Current participation in any other investigational trial. 7. Participants have undergone skin punch biopsies on the target lesion within 14 days of INV043 PDT. 8. Participants with a history of sensitivity to any of the components in the IP formulation. 9. Evidence of dermatological disease or histological evidence of a confounding skin condition in the treatment area, including but not limited to superficial BCC, worse level/grade of BCC, rosacea, psoriasis, atopic dermatitis, eczema, or any other tumour in the treatment area. 10. Evidence of xeroderma pigmentosa or other genetic dermal conditions. 11. Participants with a diagnosis of porphyria. Participants with a history of photodermatosis. 13. Use of drugs with phototoxic or photoallergic potential. 14. Treatment for any of the target lesions within 60 days of screening visit by any of the following treatments: Liquid nitrogen, Photochemotherapy (psoralene and ultraviolet A radiation, PUVA), long wave ultraviolet radiation (UVB light), surgical excision or curettage within 2 cm of target lesion; Systemic retinoids; Ionizing radiation or intralesional injections or; Undergone a skin resurfacing procedure, i.e., chemical peel, laser resurfacing, dermabrasion within the last 30 days. 15. Treatment with the following topical agents within 30 days prior to the screening visit: methyl aminolevulinate, aminolevulinate, 5-fluorouracil, corticosteroids, retinoids, diclofenac, hyaluronic acid, imiquimod. 16. History of recurrence of the target lesion. Participants with recurrent target lesion may be allowed on a case-by-case basis in discussion with study Sponsor if deemed unlikely to put participant at a higher risk of treatment- related toxicity and/or interfere with the integrity of study outcome. 17. Systemic use of immunosuppressive drugs of > 10mg Prednisolone equivalent within 30 days prior INV043 PDT. Topical, inhaled, or limited duration steroid use, e.g., for contrast allergy prophylaxis, may be allowed on a case-by-case basis in discussion with study Sponsor if deemed unlikely to put participant at a higher risk of treatment-related toxicity and/or interfere with the integrity of study outcome. 18. Use of therapeutic anti-coagulant, including prophylactic anti-platelet therapy, that cannot be safely withheld for 14 days prior to and following INV043 PDT administration. 19. QTc interval > 450 ms (male) or > 470 ms (female). 20. Known or history of, or positive test result for, hepatitis B or C, human immunodeficiency virus (HIV), syphilis or tuberculosis. 21. Uncontrolled clinically significant medical issues such as cardiac or pulmonary disease, or an uncontrolled intercurrent illness including, but not limited to, uncontrolled infection requiring systemic therapy, uncontrolled diabetes mellitus, disseminated intravascular coagulation, psychiatric illness/social situations that would limit compliance with study requirements, or other conditions that may impair wound healing. 22. Any medical condition which, in the opinion of the Investigator, places the participant at an unacceptably high risk for toxicities or adverse clinical outcome.
Outcome results
None listed