Phase II Prospective Cohort Study of Intravesical Recombinant Human Type 5 Adenovirus Injection for Treatment of High-Risk Non-Muscle Invasive Bladder Cancer: Evaluating Efficacy and Safety

NCT07356791 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT-2024-0218
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, open label, single center clinical study on the use of recombinant human adenovirus type 5 injection for bladder instillation therapy in high-risk non muscle invasive bladder urothelial carcinoma patients. The study was administered in a dose escalation manner, starting from a relatively safe dose of 1.0 × 10 \^ 12vp as the first dose group, and a 6-week DLT observation period was set up to ensure the safety of the study. Expected to enroll 12-18 participants. The subjects need to undergo maximum transurethral resection of the bladder (TURBT) and imaging diagnosis, and biological samples such as blood, urine, and biopsy tissue should be collected before treatment. The patient will receive bladder instillation therapy with recombinant human adenovirus type 5 injection after TURBT surgery. The subjects should receive a fixed dose of recombinant human adenovirus type 5 injection (1.0 × 10 \^ 12 vp or 2.0 × 10 \^ 12 vp or 3.0 × 10 \^ 12 vp) per week via bladder instillation for 6 weeks for induction therapy, followed by maintenance infusion of the same dose once a week for 3 weeks after the first induction infusion at 3, 6, 12, 18, and 24 months. After the first intravesical intervention for 3 months, tumor site pathology, imaging, and cytology will be obtained through diagnostic TURBT for tumor evaluation. Patients who achieve complete remission will maintain the same induction cycle, and will receive follow-up every 3 months for 2 years, every 6 months for more than 2 years, and once a year for more than 3 years. Patients who are intolerant to intravesical treatment (evaluated by the researchers) will be directly discontinued.

Conditions

Bladder (Urothelial, Transitional Cell) Cancer

Keywords

High-risk non-muscle invasive bladder cancer (HR-NMIBC); Bladder carcinoma in situ (CIS); Intravesical adenovirus therapy

Outcome Measures

Primary Outcomes (3)

• 3-month CR

  Complete response (CR) rate of patients receiving bladder instillation of recombinant human adenovirus type 5 injection at 3 months in each dose group.CR is defined as negative urine cytology examination, no tumor detected on imaging, and negative biopsy in the ITT population. Subjects with no response data in the primary analysis population (FAS) will be counted as non responders. Analyze based on the effectiveness analysis set

  3 months

• DLT

  DLT is defined as any of the following events related to the study drug that occur during the DLT observation period (grading criteria refer to NCI CTCAE 5.0): 1. Hematological toxicity: * Grade 4 neutrophil count decrease lasting\>5 days; -≥ Grade 3 febrile neutropenia; * Grade 4 anemia; * Grade 4 platelet count decreased; * Grade 3 platelet count decrease lasting\>7 days; * Grade 3 platelet count decrease accompanied by significant clinical bleeding symptoms; * The decrease in lymphocyte count at level 4 lasts for ≥ 14 days. 2. Liver toxicity: * Level 4 ALT or AST elevation; * Level 3 ALT or AST elevation accompanied by ≥ level 2 TBIL elevation; 3. Urinary tract related adverse reactions: -Bladder perforation or urinary fistula; -≥ grade 3 urinary tract infection, bladder spasm, cystitis, hematuria, urinary retention, urinary pain, urinary incontinnence, and lasted for\>7 days after symptomatic treatment. 4. Other non hematological toxicities: * Other non hematological toxicities of grade ≥ 3.

  6 weeks

• MTD

  This study will adopt dose escalation, starting from the initial dose group, with at least 3 cases in each dose group. If no DLT occurs, it will be raised to the next dose group; If one case of DLT occurs, three cases will be re enrolled in the same dose group. If the three newly enrolled cases do not have DLT, they will be promoted to the next dose group. Otherwise, the dose escalation experiment will be stopped. This dose level is the MTD

  6 weeks

Secondary Outcomes (8)

• AEs

  12 months

• DoR

  24 months

• 6-month CR

  6 months

• 12-month CR

  12 months

• RFS

  24 months

Other Outcomes (5)

• Biomarkers

  12 months

• Drug Recovery in Instillation Fluid and Urine

  12 months

• PK parameter

  12 months

Study Arms (1)

Single Arm

EXPERIMENTAL

The administration cycle of this experiment includes 6 induction perfusion periods (once a week for 6 consecutive weeks) and 15 maintenance perfusion periods (once a week for the first 3 weeks after 3, 6, 12, 18, and 24 months of initial induction perfusion, for a total of 3 times a month). This study will adopt the "3+3" principle for dose escalation until DLT is determined. The DLT observation period is 6 weeks before the induction perfusion period. This experiment will preset three dose groups: 1 × 1012vp, 2 × 1012vp, and 3 × 1012vp.

Drug: Recombinant Human Adenovirus Type 5 injection

Interventions

Recombinant Human Adenovirus Type 5 injection DRUG

The administration cycle of this experiment includes 6 induction perfusion periods (once a week for 6 consecutive weeks) and 15 maintenance perfusion periods (once a week for the first 3 weeks after 3, 6, 12, 18, and 24 months of initial induction perfusion, for a total of 3 times a month). This study will adopt the "3+3" principle for dose escalation until DLT is determined. The DLT observation period is 6 weeks before the induction perfusion period. This experiment will preset three dose groups: 1 × 10\^12vp, 2 × 10\^12vp, and 3 × 10\^12vp.

Single Arm

Eligibility Criteria

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

You may qualify if:

• Voluntarily participate in this clinical study, understand the study procedures, and provide written informed consent.
• Aged ≥18 years, regardless of gender.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
• Expected survival time ≥2 years.
• Histologically confirmed high-risk non-muscle invasive bladder cancer (NMIBC) ("high-risk" defined in Appendix 1 ).
• No residual lesions after cystoscopy or transurethral resection of bladder tumor (TURBT) within 6 weeks prior to the first dose, or residual lesions limited to carcinoma in situ (CIS).
• Adequate Hematologic and Organ Function :
• Hematologic (no blood transfusion, growth factors, or hematopoietic stimulants within 14 days):
• Absolute neutrophil count (ANC) ≥1.0×10⁹/L; Platelet count (PLT) ≥100×10⁹/L; Hemoglobin (Hb) ≥80 g/L.
• Liver Function :
• Total bilirubin (TBIL) ≤2×ULN; Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3×ULN.
• Renal Function :
• Serum creatinine (Cr) ≤1.5×ULN.
• Electrocardiogram (ECG) :
• QTc interval ≤450 ms (male) or ≤470 ms (female), corrected by Fridericia's formula (QTc = QT/(RR⁰·³³)).

You may not qualify if:

• Prior Bladder Radiotherapy
• Prior Treatments Without Disease Progression (as Assessed by Investigator)
• Previous intravesical therapy with cytotoxic chemotherapy or other agents (e.g., oncolytic viruses, IL-2).
• Systemic chemotherapy, immune checkpoint inhibitors, or antibody-drug conjugates (ADCs).
• Participation in other investigational drug trials for NMIBC.
• Intravesical Bacillus Calmette-Guérin (BCG) treatment within 2 weeks before the first dose (eligible if washout period exceeds 2 weeks).
• Currently receiving investigational treatment in another clinical trial or completion of such treatment \<4 weeks before the first dose in this study.
• Upper urinary tract or urethral tumors detected during screening ( CTU/MRU ). Other malignancies within 5 years before the first dose (exceptions: completely resolved carcinoma in situ or indolent malignancies like prostate cancer, per investigator's judgment).
• Active severe infections requiring IV antibiotics, antivirals, or antifungals. Grade ≥3 urinary tract infection (UTI) not recovered to Grade ≤2.
• Previous BCG therapy discontinued due to adverse events (e.g., sepsis, systemic infection, urinary incontinence) unless fully recovered to Grade ≤2 .
• Clinically Significant Cardiovascular Disease , including but not limited to:
• Congestive heart failure ( NYHA Class \>2 ); Unstable angina; Severe myocardial infarction within 6 months ; Symptomatic arrhythmias requiring intervention.
• Immunodeficiency or Transplant History , including HIV-positive serology and other acquired/congenital immunodeficiencies.
• History of organ transplantation or current immunosuppressant use.
• Active Viral Hepatitis Hepatitis B : HBeAg-positive and HBV DNA ≥500 IU/mL. Hepatitis C : Anti-HCV-positive and HCV RNA above the lower limit of detection.

Sponsors & Collaborators

• RenJi Hospital: lead

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The administration cycle of this experiment includes 6 induction perfusion periods (once a week for 6 consecutive weeks) and 15 maintenance perfusion periods (once a week for the first 3 weeks after 3, 6, 12, 18, and 24 months of initial induction perfusion, for a total of 3 times a month). This study will adopt the "3+3" principle for dose escalation until DLT is determined. The DLT observation period is 6 weeks before the induction perfusion period. This experiment will preset three dose groups: 1 × 10\^12vp, 2 × 10\^12vp, and 3 × 10\^12vp.

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: January 21, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 21, 2026

Record last verified: 2026-01