Clinical Study of T3011 Intravesical Instillation for Treatment of NMIBC Patients

NCT06427291 | Recruiting Phase 1

• 1 other identifier: MVR-T3011-ES-EC61-UC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, single-arm investigator-initiated clinical study. It is used to evaluate the safety and efficacy of T3011 intravesical instillation in patients with BCG-failure high-risk non-muscle invasive bladder cancer (NMIBC)

Conditions

Bladder Cancer

Keywords

high-risk non-muscle invasive bladder cancer (NMIBC); BCG failure or intolerance

Outcome Measures

Primary Outcomes (11)

• CR rate or relapse-free survival rates at 3, 6, 9 and 12 months after the first study dose

  Defined as the rate of Complete response or relapse-free survival at 3, 6, 9 and 12 months after first study drug administration

  3, 6, 9 and 12 months after first study dose

• Recurrence-free survival, RFS

  Defined as relapse-free survival time

  Up to 2 years

• Progression-free survival, PFS

  Defined as time to progression-free survival

  Up to 2 years

• Incidence of radical cystectomy

  Defined as the rate at which radical cystectomy occurs

  Up to 2 years

• 5-year survival rate

  Defined as survival rate at 5 year of administered treatment

  Up to 5 years

• Adverse Events, AE

  Evaluation standard is CTCAE V5.0

  up to 30 days after completion of treatment

• Serious Adverse Event, SAE

  Evaluation standard is CTCAE V5.0

  up to 30 days after completion of treatment

• Dose-limiting toxicity (DLT) events

  Defined as a toxic reaction related to the test drug occurring within the first cycle of treatment, i.e. within 28 days of the first instillation

  First cycle of treatment, i.e. within 28 days of first instillation

• Abnormal clinically significant vital signs and their incidence

  Abnormal clinically significant vital signs and their incidence

  Up to 1 years

• Abnormal clinically significant physical findings and their incidence

  Abnormal clinically significant physical findings and their incidence

  Up to 1 years

• Abnormal clinically significant laboratory findings and their incidence

  Abnormal clinically significant laboratory findings and their incidence

  Up to 1 years

Study Arms (1)

Herpes virus T3011 injection

EXPERIMENTAL

T3011 with the dose of 5 x 10\^7 PFU, 5 x 10\^8 PFU or 2 x 10\^9 PFU is administered via intravesical instillation, once a week (QW) for the first 12 weeks and then every 2 weeks (Q2W) until 12 months.

Biological: Herpes virus T3011 injection

Interventions

Herpes virus T3011 injection BIOLOGICAL

T3011 will be instilled in the entire solution volume of 50ml, and be will be left in the bladder for at least 1 hour, no more than 2 hours. After competing instillation, the patients should be instructed to drink at lest 1000mL of water

Herpes virus T3011 injection

Eligibility Criteria

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

You may qualify if:

• Participants who understand and voluntarily sign the written ICF, and are willing and able to comply with all trial requirements.
• Male or female, aged ≥ 18 years at the time of signing the ICF.
• Participants with a histologically confirmed diagnosis of NMIBC (Ta, T1 and/or Tis).
• Participants with high risk NMIBC who have been diagnosed by cystoscopy, urine cytology, and histopathology within 8 weeks prior to the first dose administration and have failed or intolerant to BCG treatment after TURBT surgery, and are not suitable or willing to undergo radical cystectomy.
• BCG-failure include BCG refractory, recurrence or relapsing after BCG treatment, BCG unresponsive and BCG intolerant.
• All tumors should have no visible tumors after transurethral bladder tumor resection (TURBT). If meeting the requirements for secondary resection, secondary resection need to be done. It is recommended to perform secondary resection if the following conditions are met: the first TURBT is insufficient, there is no muscle tissue in the first resection specimen (excluding low-grade \[Ta G1\] tumors and pure in situ cancers), T1 stage tumors, and high-grade \[G3\] tumors (excluding pure in situ cancers); Secondary resection is recommended to be performed 2-6 weeks after the first resection; Participants undergoing secondary resection must meet the requirement of no visible tumors after surgery.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Expected survival ≥3 months.
• Sufficient hematology and terminal organ function were met within 4 weeks prior to the first s treatment, for example, having sufficient bone marrow reserves and organ function:
• Hematology (hematopoietic growth factor treatment or blood transfusion should not be given within 2 weeks prior to the treatment of study drug): ANC≥1.5×10\^9/L, PLT count ≥75×10\^9/L, Hemoglobin (HGB) ≥90 g/L.
• Renal function: Creatinine clearance ≥60 mL/min (based on Cockcroft-Gault equation for calculation)
• Hepatic function: Serum total bilirubin (TBIL) ≤1.5×ULN, Aspertate aminotransferase (AST) and alanine transaminase (ALT) ≤3×ULN
• Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN; Activated partial thromboplastin time (aPTT) ≤1.5×ULN
• Women with fertility should agree to use contraceptive measures (such as intrauterine devices (IUDs), contraceptives, or condoms) during the study period and within 6 months after the end of the study; Within 7 days prior to enrollment in the study, the serum or urine pregnancy test was negative and must be a non lactating patient; Men should agree to patients who must use contraceptive measures during the study period and within 6 months after the end of the study period. Note: A female subject with fertility is defined as a female subject who has not reached a postmenopausal state after menarche (continuous amenorrhea for at least 12 months, with no other clear cause other than menopause), and has not undergone surgery (i.e. bilateral ovariectomy, fallopian tube resection, and/or hysterectomy) or other causes determined by the researcher (such as underdeveloped Mullerian tubes) leading to permanent infertility.

You may not qualify if:

• Patients meeting one or more of the following criteria will be excluded:
• The diagnosis is confirmed as muscle invasive bladder cancer (T2-T4).
• Patients with concurrent upper and lower urinary tract epithelial carcinoma, lymph node metastasis, or distant metastasis.
• Pregnant and lactating female patients.
• Having major surgery within 4 weeks prior to the first dose of the study drug, or anticipate the need for major surgery rather than diagnosis after enrolling the study.
• In addition to immediate instillation therapy after TURBT surgery, anti-tumor drug treatments such as chemotherapy, radiation therapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, etc. have been received within 4 weeks prior to the first dose of the study drug (excluding nitroso urea, mitomycin C, oral fluorouracil, small molecule targeted drugs, and traditional Chinese medicine with anti-tumor indications). Nitrso urea or mitomycin C is within 6 weeks prior to the first use of the study drug, and oral fluorouracil and small molecule targeted drugs are within 2 weeks prior to the first use of the study drug or within 5 half-lives of the drug (whichever is longer). Traditional Chinese medicine with anti-tumor indications is within 2 weeks prior to the first dose of the study drug.
• Patients who have received systemic corticosteroids (prednisone\>10mg/day or equivalent doses of similar drugs) or other immunosuppressive treatments within 14 days prior to the first dose of the study drug; Excluding the use of local, ocular, intra-articular, intranasal, and inhaled corticosteroids for treatment; Short term use of corticosteroids for preventive treatment (such as preventing contrast agent allergies).
• Taking live attenuated vaccines within 4 weeks prior to the first dose of the study drug, or it is expected that live attenuated vaccines will be vaccinated during the study period.
• Participants who have previously received oncolytic virus therapy (such as T-vec, T3011, etc.), gene therapy, cell therapy, and tumor vaccines.
• Participants have a history of splenectomy or organ transplantation.
• Participants with the malignant tumors other than the disease treated in this study, except for the following:
• Malignant tumors that have undergone treatment with the aim of cure, at least more than 5 years from the drug treatment, have no known active diseases, and have a low potential risk of recurrence;
• Fully treated non-melanoma skin cancer or malignant freckle like nevi with no evidence of disease;
• In situ cancer with sufficient treatment and no evidence of disease.
• All toxicities caused by prior radiotherapy, chemotherapy or other treatments have recovered to Grade ≤1 (CTCAE 5.0) (except for alopecia), including but not limited to urinary tract infection, urinary tract irritation, and gross hematuria.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Dingwei Ye, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dingwei Ye, Doctor

CONTACT

021-64175590; dwyeli@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 23, 2024
• Study Start: September 21, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)