Trial Title:
Clinical Study of T3011 Intravesical Instillation for Treatment of NMIBC Patients
NCT ID:
NCT06427291
Condition:
Bladder Cancer
Conditions: Official terms:
Urinary Bladder Neoplasms
Conditions: Keywords:
high-risk non-muscle invasive bladder cancer (NMIBC)
BCG failure or intolerance
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Herpes virus T3011 injection
Description:
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
Arm group label:
Herpes virus T3011 injection
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)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants who understand and voluntarily sign the written ICF, and are willing
and able to comply with all trial requirements.
2. Male or female, aged ≥ 18 years at the time of signing the ICF.
3. Participants with a histologically confirmed diagnosis of NMIBC (Ta, T1 and/or Tis).
4. 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.
5. BCG-failure include BCG refractory, recurrence or relapsing after BCG treatment, BCG
unresponsive and BCG intolerant.
6. 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.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
8. Expected survival ≥3 months.
9. 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
10. 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.
Exclusion Criteria:
Patients meeting one or more of the following criteria will be excluded:
1. The diagnosis is confirmed as muscle invasive bladder cancer (T2-T4).
2. Patients with concurrent upper and lower urinary tract epithelial carcinoma, lymph
node metastasis, or distant metastasis.
3. Pregnant and lactating female patients.
4. 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.
5. 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.
6. 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).
7. 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.
8. Participants who have previously received oncolytic virus therapy (such as T-vec,
T3011, etc.), gene therapy, cell therapy, and tumor vaccines.
9. Participants have a history of splenectomy or organ transplantation.
10. 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.
11. 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.
12. Indwelling ureteral stent or having a history of bladder ureteral reflux disease.
13. Major cardiovascular diseases, such as New York Heart Association heart disease
(grade II or higher), myocardial infarction within the first three months of
enrollment, unstable arrhythmia or unstable angina.
14. Having the history of autoimmune diseases, including but not limited to myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wagner's granulomatosis, Sjogren's syndrome, Guillain
Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Except for
patients with hypothyroidism or diabetes who have good control of alternative
treatment.
15. Persistent or active infections exist, and drug treatment and control are still not
ideal; Including but not limited to: active pulmonary tuberculosis, non negative
AIDS virus (HIV) antibody, positive hepatitis B surface antigen (HBsAg), hepatitis B
virus deoxyribonucleic acid (HBV DNA) quantity ≥ the lower limit of the laboratory
test in the research center, hepatitis C virus antibody (HCV Ab) positive and
hepatitis C virus RNA quantity ≥ the lower limit of the laboratory test in the
research center.
16. Participants who require oral or intravenous use of anti herpesvirus drugs during
the study period (including but not limited to acyclovir, valaciclovir, penciclovir,
famciclovir, ganciclovir, foxinkane, cedofovir, etc.) (excluding local use such as
topical use).
17. Participants with the history of allergic reactions to HSV-1, IL-12, or anti PD-1
antibodies and similar biological components, or those known to have allergic
reactions to any component of T3011.
18. Fever above 38.5 ℃ with no explained reason during the screening period, washout
period/baseline period, or on the day of administration (the researcher determines
that fever caused by tumors can be included), according to the researcher's
judgment, may affect the patient's participation \in this trial or interfere with
the evaluation of efficacy.
19. In the period of recurrent herpes simplex virus infection, there are corresponding
clinical manifestations, such as lip herpes, herpetic keratitis, herpetic
dermatitis, genital herpes, etc.
20. Participants who have previously developed non infectious pneumonia/interstitial
pneumonia or are intolerant to immunotherapy drugs (including but not limited to
anti PD-1/PD-L1 antibodies) (including but not limited to developing ≥ grade 3
immune related adverse events [irAEs]) (excluding endocrine related irAEs that can
be stably controlled through hormone replacement therapy).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Dingwei Ye, Doctor
Phone:
021-64175590
Email:
dwyeli@163.com
Start date:
September 21, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06427291
