Brief Title: Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming With Intradermal BCG Before Intravesical Therapy for BCG-Naive High-Grade Non-muscle Invasive Bladder Cancer

INTRODUCTION

• Org Study ID: S1602
• Secondary ID: NCI-2016-00451, S1602, S1602, U10CA180888
• NTC ID: NCT03091660
• Sponsor: Southwest Oncology Group

BRIEF SUMMARY

This randomized phase III trial studies Tokyo-172 strain bacillus Calmette-Guerin (BCG)
solution with or without a vaccination using Tokyo-172 strain BCG to see how well it works
compared with TICE BCG solution in treating patients with bladder cancer that has not spread
to muscle. BCG is a non-infectious bacteria that when instilled into the bladder may
stimulate the immune system to fight bladder cancer. Giving different versions of BCG with
vaccine therapy may prevent bladder cancer from returning.

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DETAILED DESCRIPTION

PRIMARY OBJECTIVES:

I. To compare whether time to high grade recurrence (TTHGR) for patients with BCG-naïve,
non-muscle invasive bladder cancer (NMIBC) receiving Tokyo-172 BCG strain (Arm II) is
non-inferior to patients receiving TICE BCG strain (Arm I).

II. To test whether TTHGR for patients with BCG-naïve, NMIBC receiving intradermal Tokyo-172
BCG vaccination followed by intravesical Tokyo-172 BCG instillation (Arm III) is superior to
patients receiving intravesical Tokyo-172BCG instillation without prior intradermal BCG
vaccination (Arm II).

SECONDARY OBJECTIVES:

I. To compare time to recurrence (TTR) with any-grade (AG) bladder cancer between patients
receiving Tokyo-172 versus TICE BCG strain.

II. To compare TTR with AG bladder cancer between patients receiving intradermal +
intravesical versus intravesical only Tokyo-172 BCG.

III. To compare progression-free survival (PFS) between patients receiving Tokyo-172 versus
TICE BCG strain.

IV. To compare PFS between patients receiving intradermal + intravesical versus intravesical
only Tokyo-172 BCG.

V. To compare 6-month complete response in patients with carcinoma in situ (CIS) with or
without Ta or T1 cancer present at baseline receiving Tokyo-172 versus TICE BCG strain.

VI. To compare 6-month complete response in patients with CIS with or without Ta or T1 cancer
present at baseline receiving intradermal + intravesical versus intravesical only Tokyo-172
BCG.

TERTIARY OBJECTIVES:

I. To test the hypothesis that purified protein derivative (PPD) test conversion (positive
PPD at 3 or 6 months) following BCG immunotherapy will predict time to high grade recurrence
(TTHGR).

II. To test the hypothesis that urinary cytokine levels following BCG immunotherapy will
predict time to high grade recurrence (TTHGR).

III. To test the hypothesis that tumor neoantigen burden and T lymphocyte infiltration are
associated with BCG response.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I:

INDUCTION: Patients receive TICE BCG solution intravesically once a week for 6 weeks.

MAINTENANCE: Patients receive TICE BCG solution once a week for 3 consecutive weeks at months
3, 6, 12, 18, 24, 30, and 36 for up to 7 doses.

ARM II:

INDUCTION: Patients receive Tokyo-172 strain BCG solution intravesically once a week for 6
weeks.

MAINTENANCE: Patients receive Tokyo-172 strain BCG solution once a week for 3 consecutive
weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses.

ARM III:

PRIME: Patients receive Tokyo-172 strain BCG vaccine once intradermally (ID).

INDUCTION: Within 21 days, patients receive Tokyo-172 strain BCG solution as in Arm II.

MAINTENANCE: Patients receive Tokyo-172 strain BCG solution as in Arm II.

After completion of study treatment, patients are followed up for 5 years.

• Overall Status
  Recruiting
• Start Date
  February 7, 2017
• Phase
  Phase 3
• Study Type
  Interventional