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.
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
Drug | Synonyms | Arms |
---|
VAX014 | | VAX014 |
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
Name | Type | Description | Interventions |
---|
VAX014 | Experimental | Intravesical VAX014 (dose: 3.33x10^10 - 9.0x10^11 recombinant bacterial minicells (rBMCs)), given once per week for Weeks 1-6 | |
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 prior resection, more than 3 months
from completion of last intravesical therapy with BCG, and more than 6 weeks from
completion of last therapeutic intravesical therapy with chemotherapy
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 16, 2020