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

Primary Purpose

Urothelial Carcinoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MV-NIS

About this trial

This is an interventional treatment trial for Urothelial Carcinoma focused on measuring Bladder cancer, TURBT, Radical cystectomy, BCG, Muscle Invasive Bladder Cancer, Intravesical, chemotherapy for bladder cancer, Oncolytic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

University of Miami
Ochsner Health
Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intravesical MV-NIS therapy prior to radical cystectomy

Arm Description

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).

Outcomes

Primary Outcome Measures

Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03)

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

Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

pT0 rate at time of cystectomy following intravesical MV-NIS therapy

Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

Full Information

NCT ID

NCT03171493

First Posted

March 24, 2017

Last Updated

June 26, 2023

Sponsor

Vyriad, Inc.

Collaborators

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT03171493

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

July 20, 2018 (Actual)

Primary Completion Date

February 11, 2021 (Actual)

Study Completion Date

May 12, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vyriad, Inc.

Collaborators

Mayo Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urothelial Carcinoma

Keywords

Bladder cancer, TURBT, Radical cystectomy, BCG, Muscle Invasive Bladder Cancer, Intravesical, chemotherapy for bladder cancer, Oncolytic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intravesical MV-NIS therapy prior to radical cystectomy

Arm Type

Experimental

Arm Description

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).

Intervention Type

Biological

Intervention Name(s)

MV-NIS

Intervention Description

Attenuated measles virus encoding NIS (MV-NIS)

Primary Outcome Measure Information:

Title

Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03)

Description

Assessment of safety and toxicity of intravesical MV-NIS administration in patients with Urothelial Carcinoma undergoing cystectomy

Time Frame

30 days after cystectomy

Secondary Outcome Measure Information:

Title

Pathologic staging at time of cystectomy following intravesical MV-NIS therapy

Description

Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

Time Frame

Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration)

Title

pT0 rate at time of cystectomy following intravesical MV-NIS therapy

Description

Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

Time Frame

Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alice Bexon, MD

Organizational Affiliation

CMO - Medical Monitor

Official's Role

Study Director

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Ochsner Health

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70121

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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