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

NCT ID: NCT03854721

Last Updated: 2023-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-10
• Study Completion Date: 2023-03-01

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.

Conditions

Urothelial Carcinoma of the Urinary Bladder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VAX014

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

Group Type: EXPERIMENTAL

VAX014

Intervention Type: DRUG

Solution for intravesical infusion, 3.33x10\^10 rBMCs per vial

Interventions

VAX014

Solution for intravesical infusion, 3.33x10\^10 rBMCs per vial

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vaxiion Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Urology Center of Colorado

Denver, Colorado, United States

University of Iowa Hospital and Clinics

Iowa City, Iowa, United States

New Jersey Urology, LLC.

Edison, New Jersey, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

VX0116

Identifier Type: -

Identifier Source: org_study_id