Clinical Trials /

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

NCT03171493

Description:

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.

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: VYR-MV1-102
  • NCT ID: NCT03171493

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
MV-NISIntravesical MV-NIS therapy prior to radical cystectomy

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Intravesical MV-NIS therapy prior to radical cystectomyExperimentalMV-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).
  • MV-NIS

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03)
Time Frame:30 days after cystectomy
Safety Issue:
Description:Assessment of safety and toxicity of intravesical MV-NIS administration in patients with Urothelial Carcinoma undergoing cystectomy

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy
Measure: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)
Safety Issue:
Description:Preliminary assessment of antitumor efficacy of intravesical MV-NIS therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vyriad, Inc.

Trial Keywords

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

Last Updated

June 21, 2021