Intravesical Ty21a for the Treatment of Patients With Non-muscle-invasive Bladder Cancer (NMIBC)

Non Muscle Invasive Bladder Cancer Clinical Trial

Official title:

Intravesical Ty21a for the Treatment of Patients With Non-muscle-invasive Bladder Cancer (NMIBC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03421236
• Other study ID #: IvesTy21a
• Status: Recruiting
• Phase: Phase 1
• Start date: February 18, 2018
• Est. completion date: December 1, 2022

Study information

• Verified date: April 2021
• Source: University of Lausanne Hospitals
• Contact: denise N Haefliger, PhD
• Phone: +41213144081
• Email: dnardell[@]hospvd.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bladder cancer is the fourth and eighth most common malignancy among men and women, respectively. About 75% of bladder cancers are diagnosed as non muscle-invasive and according to specific tumor-stage and grade characteristics, intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) is used to prevent recurrence and/or progression. However, BCG immunotherapy is associated with significant adverse events and treatment failure may occur in 30-40% of cases, hence the necessity for alternative therapies. In an orthotopic MB49 mouse bladder cancer model, another bacterial vaccine (Ty21a/Vivotif) turned out to be more effective than BCG for inducing tumor regression and mice survival upon intravesical instillation; and potentially safer because Ty21a bacteria did not infect/persist in any mice tissues nor in human bladder explants or cell lines, in contrast to BCG. Ty21a/Vivotif has been used in the last 30 years in millions of individuals as an oral typhoid vaccine with a high safety record. In this phase I trial we will be testing the safety of intravesical administration of Ty21a and its effect on bladder immunity in non-muscle invasive bladder cancer (NMIBC) patients, for whom recommendation of BCG therapy is not mandatory.

Description:

Escalating doses of Ty21a/Vivotif® will be administered by the intravesical route to evaluate whether Ty21 may replace the standard BCG immunotherapy in NMIBC patients.

The minimal starting dose will be instilled intravesically once a week for 4 weeks in 3 patients. If well tolerated, a 5-fold higher dose will be instilled 4-times in 3 other patients, and so on for a maximum of 4 doses to be tested.

The maximal tolerated dose will then be administered to 3 new patients 6-times once a week. If 6 instillations are well tolerated, 7 additional patients will be included to receive 6 instillations with this maximal tolerated dose.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with an intermediary or low risk of progression of bladder cancer (according to an EORTC score and clinical considerations) and thus not requiring BCG immunotherapy will be included after a transurethral resection of the bladder tumor (TURBT). Male and Female patients aged > 18yrs, with a Karnofsky performance status of 60% or more, sero-negative for HIV, HBV and HCV and with laboratory parameters for vital function in the normal range or with abnormalities without clinical significance may be included.

Exclusion Criteria:

• Patients with NMIBC that require BCG treatments or with muscle-invasive bladder cancer, sero-positive for HIV, HBV and HCV or with other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders, autoimmune disease), will be excluded.

Related Conditions & MeSH terms

• Non Muscle Invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• Ty21a
intravesical administration of Ty21a

Locations

Country	Name	City	State
Switzerland	Dpt Urology- CHUV	Lausanne	Vaud

Sponsors (1)

Lead Sponsor	Collaborator
Patrice Jichlinski

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	safety and tolerability of intravesical Ty21a	6 weeks