NCT03421236

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

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Patrice Jichlinski · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Non Muscle Invasive Bladder Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Ty21a	intravesical administration of Ty21a

Timeline

• Start date: 2018-02-18
• Primary completion: 2021-12-01
• Completion: 2022-12-01
• First posted: 2018-02-05
• Last updated: 2021-04-28

Locations

1 site across 1 country: Switzerland