IGTM-101: Suicide Plus Immune Gene Therapy for Advanced Melanoma

Sponsor

Hospital Italiano de Buenos Aires (Other)

Overall Status

Terminated

CT.gov ID

NCT03338777

Collaborator

Instituto de Oncología Ángel H. Roffo (Other), National Agency for Scientific and Technological Promotion, Argentina (Other), National Council of Scientific and Technical Research, Argentina (Other), University of Buenos Aires (Other)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: Suicide plus immunogene therapy	Early Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Suicide plus immunogene therapySuicide plus immunogene therapy

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Suicide Plus Immune Gene Therapy for Advanced Melanoma

Actual Study Start Date :

Feb 20, 2020

Actual Primary Completion Date :

Feb 20, 2020

Actual Study Completion Date :

Feb 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: Suicide plus immunogene therapy Intra and peritumoral infiltrates with multiple injections of 0.1 ml/cm2 or 0.2 ml/cm3 of lipoplexes bearing the HSVtk suicide gene (1: 1; 1 mg/ml, according to tumor size), co-administered with GCV (12.5 mg/ml). Patients start with a minimum of 0.5 ml and at the 3rd week, the maximum dose is scaled according to the tumor size up to 2 ml maximum. Treated simultaneously with a subcutaneous vaccine produced with: Formolized allogeneic tumor extracts and, Lipoplexes carrying hIL-2 and hGM-CSF genes (0.5 mg each).

Arm

Intervention/Treatment

Experimental: 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.

Biological: Suicide plus immunogene therapy

Intra and peritumoral infiltrates with multiple injections of 0.1 ml/cm2 or 0.2 ml/cm3 of lipoplexes bearing the HSVtk suicide gene (1: 1; 1 mg/ml, according to tumor size), co-administered with GCV (12.5 mg/ml). Patients start with a minimum of 0.5 ml and at the 3rd week, the maximum dose is scaled according to the tumor size up to 2 ml maximum. Treated simultaneously with a subcutaneous vaccine produced with: Formolized allogeneic tumor extracts and, Lipoplexes carrying hIL-2 and hGM-CSF genes (0.5 mg each).

Outcome Measures

Primary Outcome Measures

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.