NCT02723838

Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder

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

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Oncolytics Biotech · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Muscle-invasive Transitional Cell Carcinoma of the Bladder

Interventions

Type	Name	Description
BIOLOGICAL	REOLYSIN®	3 cycles (each cycle = 21 days). Cohort 1: 3x10E10 TCID50 intratumoral via cystoscopy on Day 1 of each cycle. Cohort 2: 3x10E10 TCID50 intratumoral via cystoscopy on Day 2 of each cycle.
DRUG	Gemcitabine	3 cycles (each cycle = 21 days). Cohort 1: 1000mg/m2 intravenously on Day 2 and Day 9 of Cycle 2 and Cycle 3. Cohort 2: 1000mg/m2 intravenously on Day 1 and Day 8 of each cycle.
DRUG	Cisplatin	3 cycles (each cycle = 21 days). Cohort 1: 70 mg/m2 intravenously on Day 2 of Cycle 2 and Cycle 3. Cohort 2: 70 mg/m2 intravenously on Day 1 of each cycle.

Timeline

• Start date: 2017-02-28
• Primary completion: 2017-09-30
• Completion: 2018-02-28
• First posted: 2016-03-31
• Last updated: 2017-03-07

Regulatory

• FDA-regulated drug study