Clinical trial · Interventional

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

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 (REBIRTH-013)

NCT07356791CI-TRIAL-00101242REBIRTH-013not yet recruitingPhase 2ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Bladder (Urothelial, Transitional Cell) Cancer	—	UNRESOLVED	—

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
Recombinant Human Adenovirus Type 5 injection	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Single Arm
description
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.
interventionNames
1. Drug: Recombinant Human Adenovirus Type 5 injection

Primary outcomes (3)

measure
3-month CR
timeFrame
3 months
description
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

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

* 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)).

Cardiac Ultrasound :

Left ventricular ejection fraction (LVEF) ≥50%.

Coagulation :

Activated partial thromboplastin time (APTT) ≤1.5×ULN; International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN. Contraception Requirements

* Non-sterilized participants of childbearing potential (male or female) must agree to use effective contraception (e.g., intrauterine device, oral contraceptives) during the study and for 3 months after treatment.

Female participants (or female partners of male participants) must use highly effective contraception.

* Non-sterilized female participants must have a negative serum HCG test within 7 days before the first dose and must not be lactating.

Exclusion Criteria:

* 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.

Hypersensitivity or Intolerance

* Known allergy or intolerance to the study drug or its excipients.
* Any other severe physical/psychiatric illness, abnormal lab results, or factors that may: Increase study participation risks; Interfere with study results; Investigator's discretion for ineligibility.

References

Publications (0)

Data not yet available

No reference posted for this study.