Muscle-invasive Transitional Cell Carcinoma of the Bladder Clinical Trial
Official title:
A Phase 1b Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
The purpose of this study is to investigate the safety and efficacy of intratumoral REOLYSIN® therapy alone and in combination with standard neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer.
Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous,
non-enveloped human reovirus. Reovirus has been shown to replicate selectively in
Ras-transformed cells causing cell lysis. Activating mutations in Ras or mutations in
oncogenes signaling through the Ras pathway may occur in as many as 80% of human tumors. The
specificity of the reovirus for Ras-transformed cells, coupled with its relatively
nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate.
This is an open-label study of intratumoral REOLYSIN® in combination with standard of care
neoadjuvant cisplatin/gemcitabine in patients with histologically and clinically confirmed
muscle-invasive bladder cancer (T2-4) with or without pelvic lymph node involvement (N1-2)
in Stage III and IV with no distant metastases (M0) and no prior systemic therapy for
bladder cancer.
Treatment with intratumoral REOLYSIN® and chemotherapy is planned for 3 cycles followed by
radical cystectomy or until unacceptable toxicity or another discontinuation criterion is
met.
Two sequential treatment cohorts will be enrolled.
Patients in Cohort 1 will receive intratumoral REOLYSIN® on Cycle 1 Day 1, then 7-14 days
later patients will receive intratumoral REOLYSIN® on Cycle 2 Day 1 plus intravenous
neoadjuvant chemotherapy for 2 cycles (every 3 weeks) starting from Cycle 2 Day 2 followed
by radical cystectomy. Three patients will be enrolled in this cohort. If there is a Dose
Limiting Toxicity the cohort will be expanded to an additional 3 patients.
Upon completion of Cohort 1, Cohort 2 will be open to enrollment of 3 patients to receive 3
cycles of standard neoadjuvant chemotherapy on Day 1 and Day 8 of each cycle and
intratumoral REOLYSIN® on Day 2 of each cycle (every 3 weeks). If there is a Dose Limiting
Toxicity the cohort will be expanded to an additional 3 patients.
An Expansion Cohort will follow with up to 12 patients to be enrolled following either
Cohort 1 or Cohort 2 treatment regimen based on the results of Cohort 1 and Cohort 2.
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