Safety, Tolerability and Pharmacokinetics Investigation of Stimotimagene Copolymerplasmid

NCT05578820 | Completed Phase 1

• 1 other identifier: NTI1GSA
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of different doses and administration regimens of Stimotimagene copolymerplasmid in patients with histologically confirmed diagnosis of solid tumor and/or its metastases.

Conditions

Sarcoma; Melanoma; Squamous Cell Carcinoma of Head and Neck; Breast Neoplasms; Uterine Cervical Neoplasms; Vulvar Neoplasms; Penile Neoplasms; Anus Neoplasms

Outcome Measures

Primary Outcomes (5)

• Safety (Presence/absence of dose-limiting toxicities (DLTs))

  Assessment of presence/absence of dose-limiting toxicities (DLTs)

  Through study completion, an average of 1 year

• Safety (Frequency and severity of adverse events (CTCAE classification))

  Assessment of frequency and severity of adverse events (CTCAE classification)

  Through study completion, an average of 1 year

• Safety (Number of cases of early termination of participation in the study due to the development of Serious Adverse Events and Other Adverse Events associated with the study therapy)

  Assessment of number of cases of early termination of participation in the study due to the development of Serious Adverse Events and Other Adverse Events associated with the study therapy)

  Through study completion, an average of 1 year

• Pharmacokinetics (Quantitative content of plasmid DNA (pTKhGM) in patients' peripheral blood)

  Assessment of quantitative content of plasmid DNA (pTKhGM) in patients' peripheral blood at: Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Days 5, 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 1st step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Days 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 2nd step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Day 7, Day 11 (before drug administration and 8 h after drug administration), Days 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 3rd step of the

  Through study completion, an average of 1 year

• Pharmacokinetics (Quantitative content of plasmid DNA (pTKhGM) in patients' urine)

  Assessment of quantitative content of plasmid DNA (pTKhGM) in patients' urine at: Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Days 5, 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 1st step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Days 7, 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 2nd step of the study; Day -1 (baseline), Day 1 (4 h and 8 h after drug administration), Day 2 (24 h after drug administration), Day 3 (48 h after drug administration), Day 6 (before drug administration and 8 h after drug administration), Day 7, Day 11 (before drug administration and 8 h after drug administration), Days 12, 17, 25, 30±3, 60±5, 90±7, 130±3 for patients from 3rd step of the study.

  Through study completion, an average of 1 year

Study Arms (3)

Dose escalation phase

EXPERIMENTAL

Stimotimagene copolymerplasmid will be administered intratumoral once in a dose of 20 mkg of DNA per 1 cm3 of tumor (for cohort 1) and 40 mkg of DNA per 1 cm3 of tumor (for cohort 2). Ganciclovir (Cimeven®) will be administrated intravenous twice a day at 12-hour intervals for 15 days.

Biological: Stimotimagene copolymerplasmid; Drug: Ganciclovir

Two times administration of Stimotimagene copolymerplasmid

EXPERIMENTAL

Stimotimagene copolymerplasmid will be administered intratumorally twice with 5-day interval in the optimal dose selected at previous stage of the trial. Ganciclovir (Cimeven®) will be administrated intravenous twice a day at 12-hour intervals for 15 days.

Biological: Stimotimagene copolymerplasmid; Drug: Ganciclovir

Tree times administration of Stimotimagene copolymerplasmid

EXPERIMENTAL

Stimotimagene copolymerplasmid will be administered intratumorally three times with 5-day interval in the optimal dose selected at first stage of the trial. Ganciclovir (Cimeven®) will be administrated intravenous twice a day at 12-hour intervals for 15 days.

Biological: Stimotimagene copolymerplasmid; Drug: Ganciclovir

Interventions

Stimotimagene copolymerplasmid BIOLOGICAL

Gene therapy drug, Intratumoral administration

Also known as: AntioncoRAN-M

Dose escalation phase; Tree times administration of Stimotimagene copolymerplasmid; Two times administration of Stimotimagene copolymerplasmid

Ganciclovir DRUG

Antiviral drug, Intravenous administration

Also known as: Cymeven®

Dose escalation phase; Tree times administration of Stimotimagene copolymerplasmid; Two times administration of Stimotimagene copolymerplasmid

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 18-75;
• Histologically confirmed diagnosis of a solid tumor and/or its metastases: Sarcoma, Melanoma, Squamous Cell Carcinoma of Head and Neck, Breast Neoplasms, Uterine Cervical Neoplasms, Vulvar Neoplasms, Penile Neoplasms, Anus Neoplasms
• Patients for whom surgery is not indicated;
• Patients with exhausted methods of drug and radiation therapy;
• Presence of clearly detectable and measurable by instrumental methods (ultrasound) tumor mass with a maximum size of at least 10 mm, palpable and accessible for intratumoral injection;
• The injected with the test drug tumor mass must not be located near large blood vessels or nerves;
• General health according to the ECOG scale 0-2;
• Life expectancy of at least 3 months;
• Hemoglobin ≥ 90 g/l;
• Absolute neutrophil count ≥ 1500/mm3;
• Platelet count ≥ 100,000/mm3;
• Creatinine clearance ≥ 70 ml/min;
• Quick Prothrombin Time more than 55%;
• At least 4 weeks or at least 5 elimination half-lives must elapse between previous chemotherapy, targeted therapy, radiotherapy, immunotherapy, or experimental antitumor therapy and administration of the study drug;
• Patients must recover from any previous surgery, radiotherapy, localized therapy, or systemic therapy to grade 1 or lower adverse reactions (except alopecia or anemia, for which grade 2 is acceptable);

You may not qualify if:

• The investigator's concern that injecting the drug into the tumor mass may lead to life-threatening side effects, if tumor swelling or inflammation occurs after treatment;
• History of hypersensitivity to ganciclovir, valganciclovir, or any other component of Cymeven®;
• History of hypersensitivity to acyclovir or pencyclovir (or their prodrugs valacyclovir or famciclovir, respectively);
• History of allergic reactions to antibiotics;
• History of allergic reaction to polyethylene glycol or polyethyleneimine;
• The following medications are scheduled to be taken during the potential therapy period:
• imipenem/cylastatin
• drugs that have myelosuppressive effects or impair renal function: nucleoside analogues (e.g., zidovudine, didanosine, stavudine), immunosuppressants (e.g., cyclosporine, tacrolimus, mycophenolate mofetil), anticancer drugs (e.g, doxorubicin, vincristine, vinblastine, hydroxyurea) and anti-infective drugs (e.g., trimethoprim/sulfamides, dapsone, amphotericin B, flucytosine, pentamidine);
• probenecid;
• Pregnancy or lactation;
• Presence of primary multiple malignant diseases;
• Presence of connection of the tumor mass with the main vessels according to ultrasound/CT/MRI data;
• Radiation damage (ulceration, necrosis);
• High risk/continued bleeding;
• Systemic connective tissue disease (scleroderma, etc.);

Sponsors & Collaborators

• Gene Surgery LLC: lead

Study Sites (4)

GBUZ Moscow Clinical Scientific Center named after Loginov MHD

Moscow, 111123, Russia

Location

FSBI N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia

Moscow, 115478, Russia

Location

FSBI National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Health of Russia

Moscow, 117997, Russia

Location

National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Moscow, 125284, Russia

Location

MeSH Terms

Conditions

Sarcoma; Melanoma; Squamous Cell Carcinoma of Head and Neck; Breast Neoplasms; Uterine Cervical Neoplasms; Vulvar Neoplasms; Penile Neoplasms; Anus Neoplasms

Interventions

Ganciclovir

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Breast Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Vulvar Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Penile Diseases; Male Urogenital Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Irina Alekseenko

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 13, 2022
• Study Start: January 1, 2022
• Primary Completion: April 11, 2024
• Study Completion: April 11, 2024
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

RU (4)