Description:
This is a Phase 1 study designed to test the tolerability and feasibility of intravesical
therapy with an attenuated Measles virus (MV-NIS) in patients with urothelial carcinoma who
are undergoing radical cystectomy but are ineligible or do not desire neoadjuvant
chemotherapy.
Title
- Brief Title: Trial of Intravesical Measles Virotherapy in Patients With Bladder Cancer Who Are Undergoing Radical Cystectomy
- Official Title: Neoadjuvant Intravesical NIS Measles Virus (MV-NIS) in Patients Undergoing Cystectomy for Urothelial Carcinoma But Ineligible for Neoadjuvant Cisplatin-based Chemotherapy
Clinical Trial IDs
- ORG STUDY ID:
VYR-MV1-102
- NCT ID:
NCT03171493
Conditions
Interventions
Drug | Synonyms | Arms |
---|
MV-NIS | | Intravesical MV-NIS therapy prior to radical cystectomy |
Purpose
This is a Phase 1 study designed to test the tolerability and feasibility of intravesical
therapy with an attenuated Measles virus (MV-NIS) in patients with urothelial carcinoma who
are undergoing radical cystectomy but are ineligible or do not desire neoadjuvant
chemotherapy.
Detailed Description
Study VYR-MV1-102 is a Phase 1 study designed to determine the tolerability, feasibility and
preliminary efficacy of attenuated MV-NIS virus after neoadjuvant intravesical administration
prior to RC in patients with UC who are ineligible for current neoadjuvant chemotherapy.
Investigators will use a novel adaptive trial design that varies the time between TURBT,
virus administration and RC.
Currently, intravesical administration of BCG is delayed four to six weeks after TURBT to
reduce the likelihood of systemic BCG absorption and BCG sepsis. Given this clinical safety
precedent, Investigators propose initial patients be treated within one week of RC to
maximize the time between TURBT and MV-NIS administration.
Subsequent patients will be treated earlier before RC (up to 29 days prior), thereby reducing
the interval between TURBT and virus administration to maximize the treatment duration before
RC. An expansion cohort will also be used to test the feasibility, tolerability and efficacy
of two repeat MV-NIS doses prior to RC. MV-NIS has been proven safe at a dose of 1x1011
TCID50 intravenously in patients lacking MV immunity (Russell 2014), which allays concern for
systemic toxicity after intravesical administration even if post-TURBT administration results
in systemic MV-NIS absorption.
Pathologic downstaging and CR (assessed by T0 rate) at surgery are secondary endpoints,
designed to give an early indication of efficacy potential. This will facilitate future
virotherapy strategies targeting replicative tumor destruction and stimulation of systemic
anti-tumor immunity as possible strategies for neoadjuvant and bladder-sparing therapy.
Trial Arms
Name | Type | Description | Interventions |
---|
Intravesical MV-NIS therapy prior to radical cystectomy | Experimental | MV-NIS will be administered via intravesical instillation as a single dose on Day 1 (7, 14, 21 or 28 days before cystectomy) or two doses on Day 1 and 15 (14 and 28 days before cystectomy). | |
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Urothelial carcinoma (UC) of the bladder, with histologic confirmation of
primary UC pathology; indication for Radical cystectomy (RC); ineligibility for
platinum-based neoadjuvant chemotherapy
- ECOG Performance Status (PS) 0 or 1.
- Ability to provide informed consent.
- Willingness to comply with all required protocol procedures including providing
biologic specimens and returning to the clinical study site for follow up visits.
- Performance status sufficient to undergo RC (in the opinion of the enrolling
urologist) including adequate hematological, liver and kidney function
- Must be willing to implement contraception throughout study and for 30 days following
RC.
Exclusion Criteria:
- Variant UC pathology including but not limited to micropapillary, signet
ring,sarcomatoid, and clear cell variants.
- Patients with any other prior malignancy are not allowed except for the following:
History of or concurrent non-invasive UC involving a portion of urinary tract outside
of the bladder; Adequately treated basal cell or squamous cell skin cancer; In situ
cervical cancer; Adequately treated Stage I or II cancer from which the patient is
currently incomplete remission or other cancer from which the patient has been
disease-free for 2 years.
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or
any other antibody or drug specifically targeting T-cell co-stimulation or immune
checkpoint pathways.
- Any of the following prior therapy: Chemotherapy ≤ 3 weeks prior to registration.
Biologic therapy ≤ 4 weeks prior to registration. Radiation therapy ≤ 3 weeks prior to
registration
- Other concurrent investigational therapy (utilized for a non-FDA-approved indication
and in the context of a research investigation).
- Pregnant women.
- Nursing women.
- Men or women of childbearing potential who are unwilling to employ adequate
contraception during treatment and 8 weeks following the completion of study drug
treatment.
- Allergy to measles vaccine or history of severe reaction to prior measles vaccination.
- History of organ transplantation.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03) |
Time Frame: | 30 days after cystectomy |
Safety Issue: | |
Description: | Assessment of safety and toxicity of intravesical MV-NIS administration in patients with Urothelial Carcinoma undergoing cystectomy |
Secondary Outcome Measures
Measure: | Pathologic staging at time of cystectomy following intravesical MV-NIS therapy |
Time Frame: | Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration) |
Safety Issue: | |
Description: | Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy |
Measure: | pT0 rate at time of cystectomy following intravesical MV-NIS therapy |
Time Frame: | Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration) |
Safety Issue: | |
Description: | Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Vyriad, Inc. |
Trial Keywords
- Bladder cancer
- TURBT
- Radical cystectomy
- BCG
- Muscle Invasive Bladder Cancer
- Intravesical
- chemotherapy for bladder cancer
- Oncolytic
Last Updated
June 21, 2021