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

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ClinicalTrials.gov Identifier: NCT03171493
Recruitment Status : Recruiting
First Posted : May 31, 2017
Last Update Posted : March 9, 2021
Sponsor:
Collaborator:
Mayo Clinic
Information provided by (Responsible Party):
Vyriad, Inc.

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.

We 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, we 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : July 20, 2018
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Measles

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)




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


Secondary Outcome Measures :
  1. 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) ]
    Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

  2. 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) ]
    Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03171493


Contacts
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Contact: Shruthi Naik, PhD 507-722-0891 snaik@vyriad.com
Contact: Barb H Duckett 507-289-0944 bduckett@vyriad.com

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Yanel Diaz    305-246-8227    YDiaz3@med.miami.edu   
Principal Investigator: Mark L Gonzalgo, MD, PhD         
United States, Louisiana
Ochsner Health Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Rachel Graham, RN    504-842-2961    rgraham@ochsner.org   
Principal Investigator: Stephen Bardot, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Tessa Kroeninger    507-538-6107    kroeninger.tessa@mayo.edu   
Principal Investigator: Bradley Leibovich, MD         
Sub-Investigator: Jack R Andrews, MD         
Sub-Investigator: Paige E Nichols, MD         
Sponsors and Collaborators
Vyriad, Inc.
Mayo Clinic
Investigators
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Study Director: Alice Bexon, MD CMO - Medical Monitor
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Responsible Party: Vyriad, Inc.
ClinicalTrials.gov Identifier: NCT03171493    
Other Study ID Numbers: VYR-MV1-102
First Posted: May 31, 2017    Key Record Dates
Last Update Posted: March 9, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vyriad, Inc.:
Bladder cancer
TURBT
Radical cystectomy
BCG
Muscle Invasive Bladder Cancer
Intravesical
chemotherapy for bladder cancer
Oncolytic
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms