Suicide Plus Immune Gene Therapy for Advanced Melanoma

Early Phase 1

Terminated

• Conditions: Melanoma
• Interventions: Biological: Suicide plus immunogene therapy

• Registration Number: NCT03338777
• Lead Sponsor: Hospital Italiano de Buenos Aires

Brief Summary

Safety evaluation of combined immunogene therapy in patients with advanced melanoma.

Detailed Description

This phase I clinical protocol is proposed to evaluate the safety of combined immunotherapy genetics in humans.

This treatment combines the high local cytotoxicity of the suicide gene system (HSV thymidine kinase: HSVt k) / prodrug (ganciclovir: GCV) with the immunostimulation of interleukin2 (hIL2) and immunoamplification of granulocyte and macrophage colony stimulating factor (hGMCSF) in the presence of tumor antigens.

The proposed scheme consists in the periodic intra / peritumoral application of plasmid DNA complexes: cationic lipid (lipoplexes) containing the HSVtk gene, co-administered with the prodrug GCV, and subcutaneous injections of a vaccine (LGvax) produced with formolized extracts of allogeneic melanoma combined with lipoplexes carrying the hIL2 and hGMCSF genes.

Study Timeline

• Study First Submitted: 2017-10-10
• Study First Submitted QC: 2017-11-08
• Study First Posted: 2017-11-09
• Status Verified: 2020-02
• Study Start: 2020-02-20
• Primary Completion: 2020-02-20
• Study Completion: 2020-02-20
• Last Update Submitted: 2020-02-21
• Last Update Posted: 2020-02-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

• Patients with histologically and / or cytologically confirmed melanoma.
• Patients progressed or are intolerant to conventional systemic treatments.
• Patients that are not candidates for surgery under oncologic criteria (complete resection).
• Performance status (ECOG) 0 or 1.
• Patients with life expectancy greater than 6 months.
• Patients with at least one accessible target lesion for gene inoculation (superficial localizations of the primary tumor, satelitosis, subcutaneous or accessible lymph node metastasis).
• Patients with measurable disease (according to RECIST 1.1 criteria, irrespective of the target lesion chosen for suicide gene inoculation)
• Patients with signed informed consent.

Exclusion Criteria

• Patients with uncontrolled cardiovascular disease

• Patients with uncontrolled respiratory disease.

• Patients with uncontrolled immune disease.

• Patients with glucocorticoids or immunosuppressive drugs or agents with immunomodulatory activity (except non-steroidal anti-inflammatory agents) up to 2 weeks before treatment.

• Patients performing other experimental therapies.

• Patients who are pregnant or breastfeeding.

• Patients undergoing concurrent chemotherapy or radiation therapy.

• Uncontrolled diabetes.

• Patients with active diagnosis of other malignant neoplasms.

• HIV-positive patients.

• Uncontrolled thyroid abnormality.

• Patients with significant medical morbidity.

• Patients with a history of allergic reactions to chemicals or similar to those used in this study.

• Metastasis in the central nervous system.

• Laboratory eligibility criteria excluded:

  • Hemoglobin: <8 g / dL, leukocytes: <3,000 / mm3, platelets: <100,000 / mm3, neutrophils: <1000 / mm3, hematocrit: <25%. bilirubin> 2.0 mg / dL, GOT or GPT: 2.5 times> than normal upper institutional limit (ULN), alkaline phosphatase: 2 times> ULN, creatinine> 2.0 mg / dL, creatinine clearence : <60 ml / min / 1.73 m2.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Suicide plus immunogene therapy	Suicide plus immunogene therapy	Intra and peritumoral infiltrates with multiple injections of lipoplexes carrying the HSVtk suicide gene co-administered with GCV and subcutaneous vaccine produced with formolized allogeneic tumor extracts and lipoplexes carrying hIL-2 and hGM-CSF genes.

Primary Outcome Measures

Name	Time	Method
Safety reported as the number of treatment-related adverse events as assessed by CTCAE v4.03	1 year	Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf).

Trial Locations

Locations (1)

Hospital Italiano; 🇦🇷 Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina