A Clinical Trial Aimed At Assessing the Efficacy and Safety of VT-101 for the Treatment of Non-muscle Invasive Bladder Cancer

NCT06632964 | Recruiting Phase 1 DMC

• 1 other identifier: XYFY2024-KL364-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is an experimental study to evaluate the efficacy and safety of VT-101 for the treatment of non-muscle invasive bladder cancer

Conditions

Non-muscle Invasive Bladder Cancer

Keywords

Oncolytic virus; Non-muscle invasive bladder cancer

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of possible adverse events after intravesical instillation of VT-101

  To evaluate the safety of VT-101 in the treatment of non-muscular invasive bladder cancer.Changes in vital signs, physical examination results, ECOG performance score, laboratory tests, and 12-lead electrocardiogram before, after, and during treatment.

  3 months after VT-101 intravesical instillation

• The proportion of patients who suspend or discontinue treatment due to drug toxicity

  Dose-Limiting Toxicity (DLT) is defined as an event related to the investigational drug that meets any of the following criteria during the observation period: Any toxicity ≥ Grade 3 except for fatigue lasting ≤3 days or fatigue and weakness that can be relieved through rest or self-adjustment; clinically insignificant reversible laboratory abnormalities ≥ Grade 3. Any toxicity that cannot recover to ≤ Grade 1 baseline level within seven days after discontinuation of dosing.

  3 months after VT-101 intravesical instillation

Secondary Outcomes (5)

• Complete Response (CR) Rate

  3 months after VT-101 intravesical instillation

• Partial Response (PR) Rate

  3 months after VT-101 intravesical instillation

• Stable Disease (SD)

  3 months after VT-101 intravesical instillation

• Progressive Disease (PD)

  3 months after VT-101 intravesical instillation

• Disease-Free Survival (DFS)

  3 months after VT-101 intravesical instillation

Study Arms (1)

VT-101

EXPERIMENTAL

The registered patients will receive oncolytic adenovirus VT-101 therapy for the non-muscle invasive bladder cancer by intravesical instillation.

Biological: Recombinant oncolytic adenovirus injection solution of VT-101

Interventions

Recombinant oncolytic adenovirus injection solution of VT-101 BIOLOGICAL

Active ingredient: VT-101 recombinant oncolytic adenovirus Specifications: 2×10\^10 IFU/ml, 0.5ml/ capsule Method of administration: intravesical perfusion

VT-101

Eligibility Criteria

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

You may qualify if:

• Age 18-75 years old (including 18 and 75 years old), male or female;
• Patients with non-muscle-invasive bladder cancer (NMIBC) confirmed by histopathological examination results (pathological stage: high-grade Ta or any T1 level papillary carcinoma or cystoscopic random biopsy confirmed presence of bladder in situ carcinoma (CIS) (with or without papillary carcinoma): according to the results of the biopsy taken within 8 weeks before the first treatment according to the study. If multiple bladder biopsies are needed to confirm eligibility, the last biopsy must be taken within 8 weeks.
• For patients with high-risk disease at the second TURBT, defined as high-grade Ta/T1 lesions, the subject must completely remove all visible tumors before enrollment and be recorded at the baseline cystoscopy.
• The results of the cellular pathology examination for high-grade urothelial carcinoma must be negative before enrollment, excluding those with unresectable high-risk and extremely high-risk NMIBC in the dose-escalation stage.
• CIS does not require complete removal, but must be completely removed along with papillary carcinoma before enrollment, and be recorded at the baseline cystoscopy. No requirement is made for negative urine cytology results for malignant cells.
• For those with unresectable high-risk and extremely high-risk NMIBC included in the dose-escalation stage, urine cytology results for malignant cells may not be required to be negative before enrollment.
• When the investigator assesses the subject as medically unfit for TURBT or radical cystectomy or the subject refuses TURBT or radical cystectomy after consulting a urologist, the subject may also participate in this study.
• Moderate, high risk and very high risk NMIBC; Specific definitions are as follows:
• Medium-risk NMIBC:
• ● Does not meet the conditions of low risk, high risk, and very high risk groups, and does not have CIS
• High-risk NMIBC:
• T1 HG/G3 tumors without CIS and not eligible for the very high risk group
• Tumors present CIS and do not meet the conditions of the very high risk group
• Ta LG/G2 or TI G1, no CIS, and three clinically relevant risk factors Ta HG/G3 or TI LG, without CIS, and with at least two clinically relevant risk causes plain
• TI G2, without CIS and containing at least one clinically relevant risk factor c.very high risk NMIBC:

You may not qualify if:

• A current or past history of muscular invasive (T2 or higher stage) or locally advanced (T3/T4, any N) or metastatic bladder cancer;
• Urothelial carcinoma of the upper urogenital tract (kidney, renal collecting system, ureter) or prostatic urethra (including urethral CIS) in the 24 months prior to enrollment;
• Cystoscopy orimaging examination confirmed the current bladder perforation;
• Prior systemic treatment, radiation therapy, or surgery for bladder cancer during screening, in addition to TURBT or bladder biopsy. Intravesical perfusion within 8 weeks prior to initiation of study therapy, with the exception of a single infusion of cytotoxic drugs (e.g. mitomycin C, gemcitabine, pirarubicin, and epirubicin) immediately after TURBT surgery;
• Past treatment with oncolytic virus drugs or similar drugs;
• Concurrent severe medical conditions, including but not limited to severe heart disease, cerebrovascular disease, uncontrolled diabetes, severe infection, active digestive ulcer, or uncontrolled high blood pressure (defined as systolic/diastolic blood pressure ≥150/100 mmHg after treatment with standardized antihypertensive drugs, or one of them); Angina pectoris in the last 3 months; Myocardial infarction or cardiac insufficiency within 1 year prior to enrollment (NYHA rating: Heart function ≥II, see Appendix 2); Severe arrhythmias requiring medical treatment; Left ventricular ejection fraction (LVEF) ≤ 50%; Adjusted for QTc interval (Fridericia formula) ≥ 480 ms, or risk factors present at the tip of torsified ventricular tachycardia, such as clinically significant hypokalemia as determined by the investigator, family history of long QT syndrome, or family history of arrhythmia (such as preexcitation complex);
• Patients who are expected to have major surgery during the study period (including the screening period);
• The subject has an active infection or unexplained fever≥ 38.5 ℃ during screening or before the first dose;
• Subject with congenital or acquired immune deficiency (such as HIV infection), syphilis antibody positive or active hepatitis B: Hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\] positive with ≥ 1000 copies of HBV-DNA \[cps\]/mL or higher than the upper limit of normal detection; Or test positive for hepatitis C antibodies, and HCV-RNA is higher than the upper limit of normal test values;
• Had received any of the following treatments within a specified time frame prior to enrollment: a. Had undergone major surgery (whether or not related to the tumor) within 4 weeks, except for minimally invasive surgery under gastroenteroscopy; b. Within 4 weeks Extended radiotherapy, or local radiotherapy within 2 weeks (investigators can determine the appropriate enrollment time based on the recovery of toxicity after radiotherapy); c. Participating in other therapeutic/interventional clinical trials within 4 weeks or currently; d. Received any local or systemic anti-tumor therapy (including anti-tumor Chinese medicines and Chinese adult drugs) within 4 weeks or within 5 half-lives of the drug (calculated as a shorter time);
• Received immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., within 2 weeks before the first dose;
• Allergic to adenovirus or any component of the test drug;
• The subject has a known history of psychotropic substance abuse, alcohol abuse, or drug use;
• History of other malignancies within the last 5 years, except cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and cured thyroid carcinoma in situ;
• Subjects with an active autoimmune disease or a history of an autoimmune disease that may recur, but subjects with the following conditions are admitted:

Sponsors & Collaborators

• The Affiliated Hospital of Xuzhou Medical University: lead
• Xuzhou Medical University: collaborator

Study Sites (1)

Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221000, China

RECRUITING

Related Publications (9)

• Chaurasiya S, Fong Y, Warner SG. Oncolytic Virotherapy for Cancer: Clinical Experience. Biomedicines. 2021 Apr 13;9(4):419. doi: 10.3390/biomedicines9040419.

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• Packiam VT, Lamm DL, Barocas DA, Trainer A, Fand B, Davis RL 3rd, Clark W, Kroeger M, Dumbadze I, Chamie K, Kader AK, Curran D, Gutheil J, Kuan A, Yeung AW, Steinberg GD. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Urol Oncol. 2018 Oct;36(10):440-447. doi: 10.1016/j.urolonc.2017.07.005. Epub 2017 Jul 26.

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• Burke JM, Lamm DL, Meng MV, Nemunaitis JJ, Stephenson JJ, Arseneau JC, Aimi J, Lerner S, Yeung AW, Kazarian T, Maslyar DJ, McKiernan JM. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. J Urol. 2012 Dec;188(6):2391-7. doi: 10.1016/j.juro.2012.07.097. Epub 2012 Oct 22.

  PMID: 23088985 BACKGROUND

• Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan TF, Hauschild A, Lebbe C, Chen L, Kim JJ, Gansert J, Andtbacka RHI, Kaufman HL. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma. J Clin Oncol. 2018 Jun 10;36(17):1658-1667. doi: 10.1200/JCO.2017.73.7379. Epub 2017 Oct 5.

  PMID: 28981385 BACKGROUND

• Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017 Sep 7;170(6):1109-1119.e10. doi: 10.1016/j.cell.2017.08.027.

  PMID: 28886381 BACKGROUND

• Andtbacka RH, Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, Delman KA, Spitler LE, Puzanov I, Agarwala SS, Milhem M, Cranmer L, Curti B, Lewis K, Ross M, Guthrie T, Linette GP, Daniels GA, Harrington K, Middleton MR, Miller WH Jr, Zager JS, Ye Y, Yao B, Li A, Doleman S, VanderWalde A, Gansert J, Coffin RS. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol. 2015 Sep 1;33(25):2780-8. doi: 10.1200/JCO.2014.58.3377. Epub 2015 May 26.

  PMID: 26014293 BACKGROUND

• Hamid O, Hoffner B, Gasal E, Hong J, Carvajal RD. Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer. Cancer Immunol Immunother. 2017 Oct;66(10):1249-1264. doi: 10.1007/s00262-017-2025-8. Epub 2017 Jul 15.

  PMID: 28712033 BACKGROUND

• Wei W, Zeng H, Zheng R, Zhang S, An L, Chen R, Wang S, Sun K, Matsuda T, Bray F, He J. Cancer registration in China and its role in cancer prevention and control. Lancet Oncol. 2020 Jul;21(7):e342-e349. doi: 10.1016/S1470-2045(20)30073-5.

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• Zheng R, Zhang S, Zeng H, Wang S, Sun K, Chen R, Li L, Wei W, He J. Cancer incidence and mortality in China, 2016. J Natl Cancer Cent. 2022 Feb 27;2(1):1-9. doi: 10.1016/j.jncc.2022.02.002. eCollection 2022 Mar.

  PMID: 39035212 BACKGROUND

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Junnian Zheng, M.D/Ph.D

  The Affiliated Hospital of Xuzhou Medical University

  STUDY DIRECTOR

• Hailong Li, M.D/Ph.D

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Meng Lu, Ph.D

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hailong Li, M.D/Ph.D

CONTACT

0086 + 13626165629; Justinlee719@163.com

Junnian Zheng, Ph.D

CONTACT

0086+15162243367

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 9, 2024
• Study Start: September 18, 2024
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: October 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)