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

February 21, 2020 updated by: Simonovich Ventura, MD, Hospital Italiano de Buenos Aires

Phase 1 Suicide Plus Immune Gene Therapy for Advanced Melanoma

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

4

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
        • Hospital Italiano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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
  1. 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.

  2. 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety reported as the number of treatment-related adverse events as assessed by CTCAE v4.03
Time Frame: 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).
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Italiano de Buenos Aires

Collaborators

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

Investigators

  • Principal Investigator: Ventura Simonovich, MD, Hospital Italiano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2020

Primary Completion (Actual)

February 20, 2020

Study Completion (Actual)

February 20, 2020

Study Registration Dates

First Submitted

October 10, 2017

First Submitted That Met QC Criteria

November 8, 2017

First Posted (Actual)

November 9, 2017

Study Record Updates

Last Update Posted (Actual)

February 25, 2020

Last Update Submitted That Met QC Criteria

February 21, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2082

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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