Trial of Intravesical Measles Virotherapy in Patients With Bladder Cancer Who Are Undergoing Radical Cystectomy

Sponsor

Vyriad, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03171493

Collaborator

Mayo Clinic (Other)

Enrollment

Locations

Arm

52.4

Anticipated Duration (Months)

5.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Urothelial Carcinoma	Biological: MV-NIS	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Intravesical NIS Measles Virus (MV-NIS) in Patients Undergoing Cystectomy for Urothelial Carcinoma But Ineligible for Neoadjuvant Cisplatin-based Chemotherapy

Actual Study Start Date :

Jul 20, 2018

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravesical MV-NIS therapy prior to radical cystectomy 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).	Biological: MV-NIS Attenuated measles virus encoding NIS (MV-NIS)

Arm

Intervention/Treatment

Experimental: Intravesical MV-NIS therapy prior to radical cystectomy

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).

Biological: MV-NIS

Attenuated measles virus encoding NIS (MV-NIS)

Outcome Measures

Primary Outcome Measures

Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03) [30 days after cystectomy]
Assessment of safety and toxicity of intravesical MV-NIS administration in patients with Urothelial Carcinoma undergoing cystectomy

Secondary Outcome Measures

Pathologic staging at time of cystectomy following intravesical MV-NIS therapy [Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration)]
Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy
pT0 rate at time of cystectomy following intravesical MV-NIS therapy [Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration)]
Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136
2	Ochsner Health	New Orleans	Louisiana	United States	70121
3	Mayo Clinic	Rochester	Minnesota	United States	55905