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

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

INTRODUCTION

  • Org Study ID: VYR-MV1-102
  • Secondary ID: N/A
  • NTC ID: NCT03171493
  • Sponsor: 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.

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.

  • Overall Status
    Recruiting
  • Start Date
    July 20, 2018
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03)

Primary Outcome 1 - Timeframe: 30 days after cystectomy

CONDITION

  • Urothelial Carcinoma

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Alice Bexon, MD

Role: Study Director

Affiliation: CMO - Medical Monitor

Overall Contact

Name: Alice Bexon, MD

Phone: 507-722-0891, 507-289-0944

Email: snaik@vyriad.com, bduckett@vyriad.com

LOCATION

Facility Status Contact
Facility: University of Miami
Miami, Florida 33136
United States
Status: Recruiting Contact: Contact
Yanel Diaz
305-246-8227
YDiaz3@med.miami.edu
Facility: Ochsner Health
New Orleans, Louisiana 70121
United States
Status: Recruiting Contact: Principal Investigator
Mark L Gonzalgo, MD, PhD
504-842-2961
rgraham@ochsner.org
Facility: Mayo Clinic
Rochester, Minnesota 55905
United States
Status: Recruiting Contact: Contact
Rachel Graham, RN
507-538-6107
kroeninger.tessa@mayo.edu