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MelanomaPhase 1/2NCT04180774

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

A Phase 1/2 study testing Tag-7 gene modified inactivated tumor cells in people with Melanoma and Kidney Cancer, run by N.N. Petrov National Medical Research Center of Oncology at 1 site in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, Kidney Cancer
What is being tested?
Tag-7 gene modified inactivated tumor cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteRussia
Study dates
31 Jan 2001to 31 Dec 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 17Show fewer
  • Platelet count < 100 × 109/L
  • Hemoglobin < 80 g/L (blood transfusions permitted)
  • History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
  • Any clinically significant unstable disease
  • Presence of symptomatic or untreated central nervous system (CNS) metastases
  • 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
  • Known history of human immunodeficiency virus infection (HIV). Testing for HIV status is not necessary unless clinically indicated
  • 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
  • Malignant disease, other than that being treated in this study
  • 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
  • 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)

Trial locations and contacts

1 site in 1 country.

Russia1 site
  • N.N. Petrov Research Institute of Oncology Chemotherapy and Innovative Technologies Department

    Saint Petersburg, 197758

Other trials in Russia

About this study

Official title: 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.

Read the 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,

Being tested
Tag-7 gene modified inactivated tumor cells
Keywords
gene modified vaccine, tag-7, immunotherapy, tumor cells-based vaccine
Medical subject headings
Melanoma, Kidney Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tag-7 gene modified inactivated tumor cellsBiological

    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.

Study groups in NCT04180774
Study groupRoleWhat they receive
Melanoma AdjuvantExperimentalPatients with completely resected stage III or IV melanoma receiving GMV in the adjuvant setting
Receives: Biological: Tag-7 gene modified inactivated tumor cells
Melanoma TherapeuticExperimentalPatients with incompletely resected stage III or IV melanoma receiving GMV in the therapeutic setting
Receives: Biological: Tag-7 gene modified inactivated tumor cells
Renal Cell AdjuvantExperimentalPatients with completely resected stage III or IV kidney cancer receiving GMV in the adjuvant setting
Receives: Biological: Tag-7 gene modified inactivated tumor cells
Renal Cell TherapeuticExperimentalPatients with incompletely resected stage III or IV kidney cancer receiving GMV in the therapeutic setting
Receives: Biological: Tag-7 gene modified inactivated tumor cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events rate

    CTC AE v.3 was used for safety assesment

    Measured: From the fist injection to 3 month after the last injection

Secondary outcomes (23)
  1. Response rate

    To assess the objective response rate (OR) RECIST v1.1 and irRC were used at the final assesment

    Measured: 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

  2. Concentration of MICA in patient's cultures supernatants

    Factor production by culture of patient's tumor cells, used for vaccine preparation

    Measured: Samples obtained before therapy start

  3. Concentration of TGF-β1 in patient's cultures supernatants

    Factor production by culture of patient's tumor cells, used for vaccine preparation

    Measured: Samples obtained before therapy start

  4. Concentration of IL-10 in patient's cultures supernatants

    Factor production by culture of patient's tumor cells, used for vaccine preparation

    Measured: Samples obtained before therapy start

  5. Concentration of VEGF in patient's cultures supernatants

    Factor production by culture of patient's tumor cells, used for vaccine preparation

    Measured: Samples obtained before therapy start

  6. Number of T-cells in peripheral blood of patients

    Absolute (10^9/L) of CD3+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  7. Number of T-helper lympocytes in peripheral blood of patients

    Absolute (10^9/L) concentration of CD4+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  8. Number of Cytotoxic lymphocytes in peripheral blood of patients

    Absolute (10^9/L) concentration of CD8+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  9. Number of NK-lymphocytes in peripheral blood of patients

    Absolute (10^9/L) concentration of CD16+CD56+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  10. Number of CD38+ cells in peripheral blood of patients

    Absolute (10^9/L) concentration of CD38+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  11. Number of HLA-DR+ cells in peripheral blood of patients

    Absolute (10^9/L) concentration of HLA-DR+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  12. Number of CD71+ cells in peripheral blood of patients

    Absolute (10^9/L) concentration of CD71+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  13. Number of B-lymphocytes cells in peripheral blood of patients

    Absolute (10^9/L) concentration of CD71+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  14. Number of CD25+ cells in peripheral blood of patients

    Absolute (10^9/L) concentration of CD25+ cells in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  15. IgA level

    IgA (g/L) level in serum

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  16. IgG level

    IgG (g/L) level in serum

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  17. IgM level

    IgM (g/L) level in serum

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  18. Spontaneous lymphocytes migration

    Lymphocytes migration (U) without stimulation

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  19. Kon-A stimulated migration

    Lymphocyte migration after in vitro stimulation with Kon A (% inhibition of migration)

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  20. PGA stimulated migration

    Lymphocyte migration after in vitro stimulation with PGA (% inhibition of migration)

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  21. Ingestion rate of monocytes

    Ingestion rate (%)

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  22. Ingestion rate of neutrophils

    Ingestion rate (%)

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

  23. Circulating immune complex level

    Immune complexes (U) in peripheral blood

    Measured: 1-5 days before each therapy cycle during course of therapy (cycle 21 days) through therapy completion, an average of 6 cycles (18 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Nov 2019
  2. Study start31 Jan 2001
  3. Primary completion31 Dec 2018
  4. Study completion31 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Studied therapy - tag-7 gene-modified vaccine (GMV) is administered intradermally at three spots (3 cm from each other) in the paravertebral area 4-6 weeks after surgery in an adjuvant or metastatic setting in patients with melanoma or kidney cancer (4 cohorts in parallel). Treatment with GMV will be administered as described until the patient experiences either unacceptable toxicity or unequivocal disease progression (PD). Biomarkers were assessed at the end of the study.
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04180774
Sponsor's protocol ID
07-Ген-М
Status last verified
Nov 2019
First submitted
22 Nov 2019
Last updated
6 Dec 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tag-7 gene modified inactivated tumor cells in people with Melanoma and Kidney Cancer, run by N.N. Petrov National Medical Research Center of Oncology at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events rate (time frame: From the fist injection to 3 month after the last injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2019.

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Clinical Trial NCT04180774 | AzTrials