Safety and Efficacy of Tag-7 Gene-modified Vaccine in Locally Advanced or Metastatic Malignant Melanoma or Kidney Cancer

December 3, 2019 updated by: N.N. Petrov National Medical Research Center of Oncology

An Open-label Study of the Safety and Efficacy of Tag-7 Gene-modified Tumor Cell-based Vaccine in Patients With Locally Advanced or Metastatic Malignant Melanoma or Renal Cell Cancer

This study was designed to assess the safety and efficacy of inactivated tumor cells genetically modified with the TAG-7 gene as immunotherapy for cancer. Patients with melanoma or kidney cancer were included since they have immune-dependent tumors. Treatment was done in the adjuvant setting after complete cytoreduction of locally advanced or metastatic disease or in the therapeutic setting in patients where complete cytoreduction was impossible.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

During the last decade, novel approaches for cancer treatment have been developed. Antitumor vaccines are one of the most promising approaches in tumor immunotherapy. Tumor cells possess low immunogenicity properties due to a number of the not completely understood mechanisms of resistance. One of the ways to overcome it is immune genes transfection. Genes encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-2 and IL-12 have been used most commonly, both in preclinical studies and clinical trials. These cytokines are well known to participate in the systemic immune response. Several studies have shown that the professional antigen-presenting cells (APCs) of the host, rather than the vaccinating tumor cells themselves, are responsible for priming CD4+ and CD8+ T cells, both of which are required to generate systemic antitumor immunity. Recent findings indicate that the adaptive arm of immunity is governed by the innate immune mechanisms that control the co-stimulatory signaling of APCs. Recently, investigators identified a novel gene, tag7, also know as PGRP-S. The insect ortholog of the tag7/PGRP-S was shown to be involved in the innate immune response in Drosophila. In preclinical studies, tag7-modified mouse tumor cells induced a long-lasting T-cell dependent immune response in mice. The effectiveness of antitumor vaccination was demonstrated on different models of mouse tumors, particularly for melanoma cells (M3, B16, F10). Clinically important results of vaccine therapy were achieved in patients with melanoma and renal carcinoma in a number of studies. The results with this treatment are comparable to chemotherapy and immunotherapy. Investigators assume that one has to activate the innate component of immunity first, followed by the activation of the adaptive one, to make anticancer vaccines more effective. Thus, a phase I/II clinical trial has been performed to evaluate the feasibility and toxicity of treatment with autologous tumor cells modified with the tag7 gene, which has been shown to be involved in innate immunity mechanisms,

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • 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

  • Russian Federation
      • St. Petersburg, Russian Federation, 197758
        • N.N. Petrov Research Institute of Oncology Chemotherapy and Innovative Technologies Department

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed inform consent form.
  2. Patients age ≥ 18 years of age at the time of informed consent.
  3. Ability to provide and understand written informed consent prior to any study procedures.
  4. Histologically confirmed locally advanced or metastatic MM or RCC.
  5. Tumor cell culture should be obtained and successfully transfected before inclusion.
  6. No evaluable therapy with a proved survival advantage in the current patient setting.
  7. The life expectancy of > 3 months as estimated by the investigator
  8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 -2 at Screening.

Exclusion Criteria:

  1. Patient with any out-of-range laboratory values defined as:

    • Serum creatinine > 1.5 × upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/minute
    • Total bilirubin > 2.5 × ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN
    • Alanine aminotransferase > 2.5 × ULN
    • Aspartate aminotransferase > 2.5 × ULN
    • Absolute neutrophil count < 1.5 × 109/L
    • Platelet count < 100 × 109/L
    • Hemoglobin < 80 g/L (blood transfusions permitted)
  2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
  3. Any clinically significant unstable disease
  4. Presence of symptomatic or untreated central nervous system (CNS) metastases
  5. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of study drug
  6. Known history of human immunodeficiency virus infection (HIV). Testing for HIV status is not necessary unless clinically indicated
  7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection
  8. Malignant disease, other than that being treated in this study
  9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive medication at any dose level, as these may interfere with the mechanism of action of study treatment. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable
  10. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation)

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Melanoma Adjuvant
Patients with completely resected stage III or IV melanoma receiving GMV in the adjuvant setting
Biological: Tag-7 gene modified inactivated tumor cells
Patients received GMV once in three weeks subcutaneously in three points in the paravertebral region. One dose consisted of 10 million transfected and inactivated tumor cells. No dose reduction was allowed.
Experimental: Melanoma Therapeutic
Patients with incompletely resected stage III or IV melanoma receiving GMV in the therapeutic setting
Biological: Tag-7 gene modified inactivated tumor cells
Patients received GMV once in three weeks subcutaneously in three points in the paravertebral region. One dose consisted of 10 million transfected and inactivated tumor cells. No dose reduction was allowed.
Experimental: Renal Cell Adjuvant
Patients with completely resected stage III or IV kidney cancer receiving GMV in the adjuvant setting
Biological: Tag-7 gene modified inactivated tumor cells
Patients received GMV once in three weeks subcutaneously in three points in the paravertebral region. One dose consisted of 10 million transfected and inactivated tumor cells. No dose reduction was allowed.
Experimental: Renal Cell Therapeutic
Patients with incompletely resected stage III or IV kidney cancer receiving GMV in the therapeutic setting
Biological: Tag-7 gene modified inactivated tumor cells
Patients received GMV once in three weeks subcutaneously in three points in the paravertebral region. One dose consisted of 10 million transfected and inactivated tumor cells. No dose reduction was allowed.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse events rate
Time Frame: From the fist injection to 3 month after the last injection
CTC AE v.3 was used for safety assesment
From the fist injection to 3 month after the last injection

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: every 8 weeks until disease progression or therapy completion, then every 3 month for 2 years, every 6 month for the next 2 years and annually thereafter
To assess the objective response rate (OR) RECIST v1.1 and irRC were used at the final assesment
every 8 weeks until disease progression or therapy completion, then every 3 month for 2 years, every 6 month for the next 2 years and annually thereafter
Concentration of MICA in patient's cultures supernatants
Time Frame: Samples obtained before therapy start
Factor production by culture of patient's tumor cells, used for vaccine preparation
Samples obtained before therapy start
Concentration of TGF-β1 in patient's cultures supernatants
Time Frame: Samples obtained before therapy start
Factor production by culture of patient's tumor cells, used for vaccine preparation
Samples obtained before therapy start
Concentration of IL-10 in patient's cultures supernatants
Time Frame: Samples obtained before therapy start
Factor production by culture of patient's tumor cells, used for vaccine preparation
Samples obtained before therapy start
Concentration of VEGF in patient's cultures supernatants
Time Frame: Samples obtained before therapy start
Factor production by culture of patient's tumor cells, used for vaccine preparation
Samples obtained before therapy start
Number of T-cells in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) of CD3+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of T-helper lympocytes in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD4+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of Cytotoxic lymphocytes in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD8+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of NK-lymphocytes in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD16+CD56+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of CD38+ cells in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD38+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of HLA-DR+ cells in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of HLA-DR+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of CD71+ cells in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD71+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of B-lymphocytes cells in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD71+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Number of CD25+ cells in peripheral blood of patients
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Absolute (10^9/L) concentration of CD25+ cells in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
IgA level
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
IgA (g/L) level in serum
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
IgG level
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
IgG (g/L) level in serum
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
IgM level
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
IgM (g/L) level in serum
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Spontaneous lymphocytes migration
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Lymphocytes migration (U) without stimulation
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Kon-A stimulated migration
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Lymphocyte migration after in vitro stimulation with Kon A (% inhibition of migration)
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
PGA stimulated migration
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Lymphocyte migration after in vitro stimulation with PGA (% inhibition of migration)
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Ingestion rate of monocytes
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Ingestion rate (%)
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Ingestion rate of neutrophils
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Ingestion rate (%)
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Circulating immune complex level
Time Frame: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)
Immune complexes (U) in peripheral blood
1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
N.N. Petrov National Medical Research Center of Oncology

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institute of Gene Biology Russian Academy of Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Georgy P Georgiev, Institute of Gene Biology of the Russian Academy of Sciences

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 31, 2001

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 22, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 26, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 6, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 3, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 07-Ген-М

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

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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