Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
- Conditions
- Muscle-invasive Transitional Cell Carcinoma of the Bladder
- Registration Number
- NCT02723838
- Lead Sponsor
- Oncolytics Biotech
- Brief 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method 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 Incidence of Treatment-Emergent Adverse Events During treatment and up to 28 days after treatment Nature, frequency, severity and timing of Adverse Events.
- Secondary Outcome Measures
Name Time Method Disease Free Survival (DFS) By medical chart review until disease reoccurrence or death or 2 years from surgery, whichever occurs first. Time to Treatment Failure (TTF) By medical chart review until disease reoccurrence or 2 years from surgery, whichever occurs first first.