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

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


  • Org Study ID: VYR-MV1-102
  • Secondary ID:
  • NCT ID: NCT03171493
  • NCT Alias:
  • Sponsor: Vyriad, Inc. - Industry
  • Source: 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.

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.

Overal Status Start Date Phase Study Type
Recruiting July 20, 2018 Phase 1 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 - Time Frame: 30 days after cystectomy

Condition:

  • Urothelial Carcinoma

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.
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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: Shruthi Naik, PhD

Phone: 507-722-0891

Email: snaik@vyriad.com

Locations

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