Clinical Trials /

A Phase 1 Study of Intravesical VAX014 for Instillation in Subjects With Non-Muscle Invasive Bladder Cancer

NCT03854721

Description:

The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for Instillation (VAX014) in patients with low-grade Non-Muscle Invasive Bladder Cancer (NMIBC). VAX014 is a targeted oncolytic agent designed to kill tumor cells following instillation into the urinary bladder.

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of Intravesical VAX014 for Instillation in Subjects With Non-Muscle Invasive Bladder Cancer
  • Official Title: Phase I Safety and Tolerability of Intravesical VAX014 for Instillation in Subjects With Non-Muscle Invasive Bladder Cancer (NMIBC)

Clinical Trial IDs

  • ORG STUDY ID: VX0116
  • NCT ID: NCT03854721

Conditions

  • Urothelial Carcinoma of the Urinary Bladder

Interventions

DrugSynonymsArms
VAX014VAX014

Purpose

The purpose of this research study is to evaluate the safety, tolerability and activity of VAX014 for Instillation (VAX014) in patients with low-grade Non-Muscle Invasive Bladder Cancer (NMIBC). VAX014 is a targeted oncolytic agent designed to kill tumor cells following instillation into the urinary bladder.

Detailed Description

      This study will evaluate the safety and tolerability of VAX014 using a 3+3 dose escalation
      design to determine a maximum tolerated dose (MTD) followed by a dose expansion at the
      Recommended Phase 2 Dose (RP2D). Both phases of the study will use a Window of Opportunity
      study design where patients with a single, low-grade Ta lesion will receive VAX014 via a
      urinary catheter into the bladder, weekly for 6 weeks prior to undergoing Transurethral
      Resection of Bladder Tumor (TURBT) to assess antitumor activity against the mapped lesion.

      Patients enrolled in this study must have low-grade (Ta) Non-Muscle Invasive Bladder Cancer.
      However, eligible patients may have up to 5 low-grade Ta lesions at screening, and all but a
      single mapped lesion will be resected prior to receiving VAX014. The mapped lesion is
      assessed for anti-tumor activity.

      VAX014 is a formulation of recombinant bacterial minicells which is designed to selectively
      target two NMIBC-associated integrin heterodimers to de-stabilize tumor cell membranes, with
      the result being tumor cell lysis.
    

Trial Arms

NameTypeDescriptionInterventions
VAX014ExperimentalIntravesical VAX014 (dose: 3.33x10^10 - 9.0x10^11 recombinant bacterial minicells (rBMCs)), given once per week for Weeks 1-6
  • VAX014

Eligibility Criteria

        Inclusion Criteria:

          1. Signed, informed consent

          2. Age 18 or more years

          3. Pathologically confirmed low-grade Ta urothelial carcinoma (UC) of the urinary bladder

          4. NMIBC with one solitary measurable tumor at the start of study, measuring ≥ 5 mm and ≤
             15 mm in greatest diameter (up to 4 additional low-grade Ta lesions, each measuring no
             more than 15 mm may be removed at screening provided a single lesion remains)

          5. Treatment-naïve or failed one previous regimen of intravesical therapy (BCG or
             chemotherapy)

          6. If recurrent disease, then more than 6 months from completion of prior therapy or
             resection

          7. If previously treated, recovered from prior treatment-related toxicity to ≤ Grade 1

          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 116

          9. Absolute neutrophil count (ANC) ≥ 1,500/mm3

         10. Platelet count ≥ 100,000/mm3

         11. Total bilirubin ≤ 1.5 x upper limit of normal (ULN), or ≤ 3 x ULN in subjects with
             Gilberts disease

         12. Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min

         13. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 2.5 x ULN

         14. Willingness to participate in collection of pharmacokinetic samples

         15. Women of childbearing potential must have a negative serum pregnancy test.

         16. All subjects of childbearing potential must be willing to use effective contraception
             while on treatment and for 3 months after the last dose of VAX014

        Exclusion Criteria:

          1. Additional papillary disease at screening (in addition to the solitary low-grade Ta
             lesion detailed in the inclusion criteria) that

               1. Consist of 6 or more lesions

               2. Consists of any lesion with a maximal diameter of greater than 15 mm

          2. Confirmed or suspected perforated bladder

          3. History of difficult catheterization that in the opinion of the investigator will
             prevent administration of VAX014

          4. Presence or history of any high-grade urothelial cancer (including CIS) or high-grade
             urine cytology

          5. Intravesical chemo-or biological therapy within 6 months of first administration of
             VAX014

          6. UC of the ureters or urethra

          7. History of interstitial cystitis

          8. History of radiation to the pelvis

          9. History of vesicoureteral reflux or an indwelling urinary stent

         10. Other known active cancer(s) likely to require treatment or interfere with study
             objectives over the next two (2) years

         11. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
             therapy

         12. Known HIV, Hepatitis B, or Hepatitis C infection

         13. Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial
             infarction within 6 months)

         14. Major surgery other than diagnostic surgery within 4 weeks of first administration of
             VAX014

         15. Pregnant or currently breast-feeding

         16. Psychiatric illness/social situations that would interfere with compliance with study
             requirements

         17. Presence of any sessile appearing tumor suspected of being invasive or high-grade
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of VAX014
Time Frame:up to 28 days
Safety Issue:
Description:The MTD will be defined as the dose level at which at most one of six patients experiences a dose limiting toxicity (DLT) after 28 days of treatment have occurred, with the next higher dose having at least 2/3 or 2/6 patients experiencing a DLT

Secondary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) of intravesical VAX014
Time Frame:up to 5 weeks
Safety Issue:
Description:The RP2D will be determined following the determination of the MTD and an overall assessment of safety as determined by the Safety Committee
Measure:Peak Plasma Concentration (Cmax)
Time Frame:Day 1
Safety Issue:
Description:The peak plasma concentration (Cmax) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Trough Plasma Concentration (Cmin)
Time Frame:Day 1
Safety Issue:
Description:The trough plasma concentration (Cmin) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Time to Peak Plasma Concentration (Tmax)
Time Frame:Day 1
Safety Issue:
Description:The time to peak plasma concentration (Tmax) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Volume and Distribution (Vd)
Time Frame:Day 1
Safety Issue:
Description:The volume and distribution (Vd) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Half Life (t[1/2])
Time Frame:Day 1
Safety Issue:
Description:The half life (t[1/2]) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Area Under Curve (AUC)
Time Frame:Day 1
Safety Issue:
Description:The area under the plasma concentration versus time curve (AUC) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Clearance (Cl)
Time Frame:Day 1
Safety Issue:
Description:The clearance (Cl) will be measured as part of pharmacokinetic (PK) testing. In the event early analysis determines that VAX014 is not detectable in whole blood, PK sampling and analysis will be suspended.
Measure:Overall Response Rate
Time Frame:Up to 20 weeks
Safety Issue:
Description:Response rate will be evaluated for low-grade Ta lesions. Lesions will be assessed with cystoscopy and change in tumor size will be recorded.
Measure:Anti-Drug Antibodies (Immunogenicity)
Time Frame:Up to 20 weeks
Safety Issue:
Description:The presence or absence of anti-drug antibodies (ADA) in serum will be assessed by assay.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vaxiion Therapeutics

Trial Keywords

  • Non-Muscle Invasive Bladder Cancer

Last Updated

November 4, 2019