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Suicide Plus Immune Gene Therapy for Advanced Melanoma (IGTM-101)

Primary Purpose

Melanoma

Status

Terminated

Phase

Early Phase 1

Locations

Argentina

Study Type

Interventional

Intervention

Suicide plus immunogene therapy

About this trial

This is an interventional treatment trial for Melanoma focused on measuring melanoma, lipoplexes, plasmid, herpes simplex thymidine kinase, interleukin-2, granulocyte-macrophage colony-stimulating factor, tumor vaccine, suicide gene

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Hospital Italiano

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Suicide plus immunogene therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety reported as the number of treatment-related adverse events as assessed by CTCAE v4.03

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).

Secondary Outcome Measures

Full Information

NCT ID

NCT03338777

First Posted

October 10, 2017

Last Updated

February 21, 2020

Sponsor

Hospital Italiano de Buenos Aires

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03338777

Brief Title

Suicide Plus Immune Gene Therapy for Advanced Melanoma

Acronym

IGTM-101

Official Title

Phase 1 Suicide Plus Immune Gene Therapy for Advanced Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Terminated

Why Stopped

Failure to achieve primary objective

Study Start Date

February 20, 2020 (Actual)

Primary Completion Date

February 20, 2020 (Actual)

Study Completion Date

February 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hospital Italiano de Buenos Aires

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

melanoma, lipoplexes, plasmid, herpes simplex thymidine kinase, interleukin-2, granulocyte-macrophage colony-stimulating factor, tumor vaccine, suicide gene

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Suicide plus immunogene therapy

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Suicide plus immunogene therapy

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Suicide plus immunogene therapy

Intervention Description

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).

Primary Outcome Measure Information:

Title

Safety reported as the number of treatment-related adverse events as assessed by CTCAE v4.03

Description

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ventura Simonovich, MD

Organizational Affiliation

Hospital Italiano

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Italiano

City

Ciudad Autónoma de Buenos Aires

State/Province

Buenos Aires

Country

Argentina

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Suicide Plus Immune Gene Therapy for Advanced Melanoma

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