Intratumoral phIL12 GET (SmartGeneH&N)

Treatment of Skin Tumours With Intratumoral Interleukin 12 Gene Electrotransfer in the Head and Neck Region

Electroporation provides non-viral gene delivery method for plasmid DNA. Its clinical application was already proven in preclinical and in clinical trial in treatment of melanoma skin metastases with plasmid coding IL-12, in USA. Intratumoral gene transfer of plasmid coding for IL-12 has proven safe end effective, having good local tumour control and some evidence indicates on abscopal effect. The EU directives recommend the use of plasmids without the gene for antibiotic resistance. For this purpose we constructed plasmid coding for IL-12 in accordance with the EU regulatory requirements.

In the proposed study we intend to study the safety and tolerability of the constructed plasmid, phIL12, in treatment of basal cell carcinomas in patients with operable tumors in head and neck region. The study is designed as exploratory, dose escalating with the aim to determine the dose of plasmid that produces IL-12 expression in the tumours with best biological activity, infiltration of the immune cells and no toxicity.

Study Overview

• Status: Completed
• Conditions: Basal Cell Carcinoma
• Intervention / Treatment: Drug: phIL12 GET

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Institute of Oncology Ljubljana
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana, Department of Otorhinolaryngology and Cervicofacial Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed, previously untreated cutaneous basal cell carcinoma located in head and neck region.
• Solitary tumors, with largest diameter up to 3 cm, in the region where curative surgery is feasible.
• Age 18-years or older.
• Life expectancy > 3 months.
• Physical performance in accordance with the Karnofsky scale ≥ 70 or < 2 in accordance with World Health Organization (WHO) scale.
• The patient must be capable of understanding the treatment procedure and possible adverse events, which may arise during treatment.
• The patient must be capable of signing the informed consent to participate in the clinical study (voluntary and conscientious consent after education).
• Prior to inclusion in the trial, the patient must be presented at a multidisciplinary advisory team meeting.

Exclusion Criteria:

• Known malignancy elsewhere in/on the body.
• Lesions not suitable for treatment with GET (invasion into the bone, infiltration of large vessels).
• A life-threatening infection and/or severe heart failure and/or liver failure and/or other life-threatening systemic diseases.
• Significantly reduced lung function, which requires the determination of DLCO. Patients should not be treated if DLCO is abnormal.
• Treatment with immunosuppressive drugs, steroids and other drugs that would affect poor wound healing.
• Age under 18-years.
• Major disruptions in the coagulation system (who does not respond to the standard therapy - replacement of vitamin K or freshly frozen plasma).
• A chronic decline in the kidney function (creatinine > 150 µmol/L).
• Epilepsy.
• Pregnancy and breast-feeding.
• The patient's incapability of comprehending the purpose or course of the trial, or not agreeing to be included in the trial.
• Patients unwilling or unable to comply with the protocol requirements and scheduled visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intratumoral phIL12 gene electrotransfer	Drug: phIL12 GET; intratumoral phIL12 gene electrotransfer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of acute adverse events	CTCAE v.5.0 criteria	Adverse events 2 days after the treatment.
Number of adverse events 7 days after the treatment	CTCAE v.5.0 criteria	Adverse events 7 days after the treatment.
Number of late adverse events	CTCAE v.5.0 criteria	Adverse events 30 days after the treatment.
Evaluating quality of life with questionnaire one week after the treatment	EORTC QLQ-C30	Changes from baseline 7 days after the treatment.
Evaluating quality of life with questionnaire one month after the treatment	EORTC QLQ-C30	Changes from baseline 30 days after the treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC)	Determination of serum levels of IL-12 cytokine.	Changes from baseline at 2, 7 and 30 days after the treatment.
Concentrations of IL-12 and IFN-y in tumor samples	Determination of tumor IL-12 and IFN-y levels in tumor biopsies.	Changes from baseline at 7 and 30 days after the treatment.

Collaborators and Investigators

• Sponsor: Institute of Oncology Ljubljana

Publications and helpful links

General Publications

• Groselj A, Bosnjak M, Jesenko T, Cemazar M, Markelc B, Strojan P, Sersa G. Treatment of skin tumors with intratumoral interleukin 12 gene electrotransfer in the head and neck region: a first-in-human clinical trial protocol. Radiol Oncol. 2022 Aug 14;56(3):398-408. doi: 10.2478/raon-2022-0021.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: October 10, 2021
• First Posted (Actual): October 13, 2021

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Basal Cell; Carcinoma, Basal Cell
• Other Study ID Numbers: ERIDEK-0086/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No