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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03854721
Recruitment Status : Recruiting
First Posted : February 26, 2019
Last Update Posted : November 6, 2019
Sponsor:
Information provided by (Responsible Party):
Vaxiion Therapeutics

Tracking Information
First Submitted Date  ICMJE February 21, 2019
First Posted Date  ICMJE February 26, 2019
Last Update Posted Date November 6, 2019
Actual Study Start Date  ICMJE May 10, 2019
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • Maximum tolerated dose (MTD) of VAX014 [ Time Frame: up to 28 days ]
    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
  • Incidence of Treatment-Emergence Adverse Events (Safety and Tolerability) [ Time Frame: Through study completion, an average of 20 weeks ]
    Toxicities will be assessed in each subject by tracking the occurrence of graded Adverse Events (AEs). AEs will be graded according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v5.0
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2019)
  • Recommended Phase 2 Dose (RP2D) of intravesical VAX014 [ Time Frame: up to 5 weeks ]
    The RP2D will be determined following the determination of the MTD and an overall assessment of safety as determined by the Safety Committee
  • Peak Plasma Concentration (Cmax) [ Time Frame: Day 1 ]
    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.
  • Trough Plasma Concentration (Cmin) [ Time Frame: Day 1 ]
    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.
  • Time to Peak Plasma Concentration (Tmax) [ Time Frame: Day 1 ]
    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.
  • Volume and Distribution (Vd) [ Time Frame: Day 1 ]
    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.
  • Half Life (t[1/2]) [ Time Frame: Day 1 ]
    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.
  • Area Under Curve (AUC) [ Time Frame: Day 1 ]
    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.
  • Clearance (Cl) [ Time Frame: Day 1 ]
    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.
  • Overall Response Rate [ Time Frame: Up to 20 weeks ]
    Response rate will be evaluated for low-grade Ta lesions. Lesions will be assessed with cystoscopy and change in tumor size will be recorded.
  • Anti-Drug Antibodies (Immunogenicity) [ Time Frame: Up to 20 weeks ]
    The presence or absence of anti-drug antibodies (ADA) in serum will be assessed by assay.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Intravesical VAX014 for Instillation in Subjects With Non-Muscle Invasive Bladder Cancer
Official Title  ICMJE Phase I Safety and Tolerability of Intravesical VAX014 for Instillation in Subjects With Non-Muscle Invasive Bladder Cancer (NMIBC)
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma of the Urinary Bladder
Intervention  ICMJE Drug: VAX014
Solution for intravesical infusion, 3.33x10^10 rBMCs per vial
Study Arms  ICMJE Experimental: VAX014
Intravesical VAX014 (dose: 3.33x10^10 - 9.0x10^11 recombinant bacterial minicells (rBMCs)), given once per week for Weeks 1-6
Intervention: Drug: VAX014
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 22, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kaitlyn Cohen, MBS 858-642-0386 ext 205 kcohen@sciquus.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03854721
Other Study ID Numbers  ICMJE VX0116
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Vaxiion Therapeutics
Study Sponsor  ICMJE Vaxiion Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Vaxiion Therapeutics
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP