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

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02723838
• Other study ID #: REO 023
• Status: Withdrawn
• Phase: Phase 1
• First received: March 24, 2016
• Last updated: March 3, 2017
• Start date: February 28, 2017
• Est. completion date: February 28, 2018

Study information

• Verified date: March 2017
• Source: Oncolytics Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 28, 2018
• Est. primary completion date: September 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph nodes involvement (N1-2) in Stage III and IV (M0).

• ECOG performance status =2.

• Adequate liver function with a bilirubin within normal limits. Transaminases up to 3 x ULN (Grade 1) and alkaline phosphatase may be up to 2.5 x ULN (Grade 1).

• Adequate bone marrow function, as defined by neutrophils count of =1,500/mm3, and platelet count =100,000/ mm3.

• Adequate renal function (serum creatinine =1.5 times the ULN).

• Negative pregnancy test and reliable and appropriate contraceptive method during the study for a woman of childbearing potential. All female patients of childbearing age and all male patients with partners of childbearing age should use a reliable method of contraception, such as the barrier method, throughout the study and for 60 days after last treatment.

• Informed of the investigational nature of this study and must sign a written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

• Received any prior therapy for invasive bladder cancer including surgery, radiation therapy, chemotherapy or any other systemic anti-cancer therapy (prior intravesical therapy for non-invasive bladder cancer is acceptable including intravesical BCG and/or mitomycin and interferon).

• Evidence of lymph nodes or other metastatic disease beyond the pelvis (N3 and/or M1).

• Pre-existing immunosuppressive or connective tissue disorders that require immune suppressive drugs.

• History of HIV or active hepatitis.

• Any serious concurrent illness including; but not limited to, unstable angina pectoris, uncompensated congestive cardiac failure; myocardial infarct in the previous 6 months; cardiac arrhythmias or psychiatric illness that would limit compliance with study requirements.

• Pregnant or lactating.

• A history of hypersensitivity to gemcitabine and cisplatin or any component of the formulation.

• A prior malignancy, other than non-melanoma skin cancer, unless they have completed therapy at least 5 years prior to start of study and have no evidence of recurrent or residual disease.

• Unwilling or unable to sign informed consent document.

• In social situations that would limit compliance with study requirements.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Muscle-invasive Transitional Cell Carcinoma of the Bladder
• Urinary Bladder Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Oncolytics Biotech

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events	Nature, frequency, severity and timing of Adverse Events.	During treatment and up to 28 days after treatment
Primary	Pre- and post-treatment biopsies will be evaluated for tumor viability, percentage of necrosis, reovirus replication and tumor infiltration of immune cells and expression of PD-1 and PD-L1		Assessed at surgery conducted following 3 3-week study treatment cycles
Secondary	Time to Treatment Failure (TTF)		By medical chart review until disease reoccurrence or 2 years from surgery, whichever occurs first first.
Secondary	Disease Free Survival (DFS)		By medical chart review until disease reoccurrence or death or 2 years from surgery, whichever occurs first.