Clinical trial NCT03719300: Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC
Official title: A Phase 2 Study of BC-819 in Patients With Non-Muscle Invasive Bladder Cancer Whose Disease is Unresponsive to Bacillus Calmette-Guerin
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-muscle Invasive Bladder Cancer (NMIBC)
Keywords: BCG-unresponsive
Lead sponsor: Anchiano Therapeutics Israel Ltd.
Sponsor class: INDUSTRY
First posted: 2018-10-25
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study, BC-819-18-204, is a Phase 2, open-label, monotherapy, single-arm, multicenter clinical trial of BC-819 (inodiftagene vixteplasmid) in patients with NMIBC adequately treated with Bacillus Calmette-Guerin (BCG) whose disease is BCG unresponsive according to the US Food and Drug Administration (FDA) guidance.

Detailed description: BC-819 (inodiftagene vixteplasmid) is a recombinant DNA plasmid that directs the expression of a potent toxin specifically in malignant cells but not in normal tissue. It has been designed to exploit the established biology of the H19 gene, which is upregulated and expressed at high levels only in malignant cells, to produce bacterial diphtheria toxin only in bladder cancer tissue. BC-819 is administered directly into the bladder to enable maximal topical exposure to target bladder cancer cells.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients ≥18 years of age at the time of consent
2. Patient must have been adequately treated with BCG defined as at least one of the following (FDA 2018):

   1. At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy
   2. At least five of six doses of an initial induction course plus at least two of six doses of a second induction course
   3. A single course of induction BCG can qualify if the patient has T1 high-grade disease at first evaluation (see 3c)
3. Patient must be BCG-unresponsive defined as at least one of the following (FDA 2018):

   1. Persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of completion of adequate BCG therapy. An assessment within 15 months can also qualify when no assessment was done 12 months after completion of adequate BCG therapy.
   2. Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy. An assessment within 9 months can also qualify when no assessment was done 6 months after completion of adequate BCG therapy.
   3. T1 high-grade disease at the first evaluation following a single course of induction BCG qualifies (Lerner et al. 2015, Steinberg et al. 2016)
4. Patient must have, at study entry, NMIBC indicated by 1 or more of the following:

   1. Ta or T1 high-grade disease
   2. CIS disease
5. Patient must have no known evidence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra within 6 months of enrollment
6. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
7. Patient must have adequate hematologic function, as demonstrated by the following:

   1. Hemoglobin level ≥10 g/dL
   2. Absolute neutrophil count ≥1.5 x 109/L
   3. Platelet count ≥100 x 109/L
8. Patient must have adequate liver and renal function as demonstrated by the following:

   1. Aspartate aminotransferase and alanine aminotransferase each ≤3.0 x upper limit of normal
   2. Total bilirubin ≤1.5 x upper limit of normal, unless prior documentation of Gilbert's syndrome in which case, 3.0 mg/dL is allowed
   3. Serum creatinine ≤1.5 x upper limit of normal or measured or calculated creatinine clearance ≥30 mL/min
9. Female patients of childbearing potential must use maximally effective birth control during the period of therapy and for 1 month after the last study drug infusion
10. Male patients who are sexually active must be willing to use a double barrier contraceptive method upon study enrollment, during the course of the study, and for 1 month after the last study drug infusion

Exclusion Criteria:

1. Patient has current or previous evidence of muscle invasive (muscularis propria) or metastatic bladder cancer disease
2. Patient has received prior investigational therapy for NMIBC
3. Patient has received any therapy for NMIBC within 10 weeks before the start of study treatment other than surgical resection, 1 dose of chemotherapy, and previous BCG
4. Patient is intolerant to previous BCG treatment in the absence of meeting other criteria for BCG unresponsiveness and adequate BCG therapy
5. Patient has received external beam radiation therapy for bladder cancer at any time or for any other condition
6. Patient has an active infection, including urinary tract infection (viral, bacterial, or fungal) and cystitis
7. Patient has urinary tract signs or symptoms that preclude retention of drug in the bladder; this does not include anticholinergic drugs
8. Patient is known to have tested positive for human immunodeficiency virus (HIV). No HIV testing is required if patient is not known have tested positive
9. Patient is female and is pregnant or breastfeeding
10. Patient has a known presence or history of malignancy of other organ system within the 5 years before study start, with the exception of non-melanoma skin cancer; very low or low-risk prostate cancer; or patients who have been disease free for at least 2 years following stage 1 or 2 cancer

Primary outcomes:
measure: The Percentage of Patients With Baseline CIS That Achieve a Complete Response After Treatment With BC-819 (Measured at 12 Weeks)
timeFrame: 12 weeks
Secondary outcomes:
measure: Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 48 Weeks (Overall Population and Subgroup of Patients With CIS)
timeFrame: 48 weeks
measure: Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 12, 24, 36, 72, and 96 Weeks (Overall Population and Subgroup of Patients With CIS)
timeFrame: 12, 24, 36, 72, and 96 weeks
measure: Percentage of Patients Who Are Progression-free at 48, 72, and 96 Weeks
timeFrame: 48, 72, and 96 weeks
measure: Overall Survival of Patients Enrolled in the Study at 48, 72, and 96 Weeks
timeFrame: 48, 72, and 96 weeks
measure: Quality of Life in Patients Treated With BC-819
timeFrame: 48, 72, and 96 weeks
measure: Assessment of Safety
timeFrame: 9 months
measure: Time to Recurrence (Kaplan-Meier Plot)
timeFrame: 12, 24, 36, 72, and 96 weeks
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Urological Institute
state: Alaska
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Los Angeles
country: United States
facility: American Institute of Research
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Jacksonville, Shands Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Urology
state: Idaho
city: Meridian
country: United States
facility: Idaho Urologic Institute, PA
state: Idaho
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Systems (Outpatient Care Center)
state: Illinois
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Wichita
country: United States
facility: Wichita Urology Group
state: Kansas
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinical Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institution
state: Maryland
city: Grand Rapids
country: United States
facility: Spectrum Health Medical Group
state: Michigan
city: Troy
country: United States
facility: Michigan Institute of Urology, PC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Belleville
country: United States
facility: New Jersey Urology, LLC
state: New Jersey
city: Voorhees
country: United States
facility: MD Anderson Cancer Center at Cooper
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - NY Presbyterian Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC Chapel Hill Hospital, Urology Clinic
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greensboro
country: United States
facility: Alliance Urology Specialists, PA
state: North Carolina
city: Huntersville
country: United States
facility: Carolina Urology Partners, PLLC
state: North Carolina
city: Toledo
country: United States
facility: University of Toledo, Dept. of Urology and Kidney Transplant
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Regional Urology
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Medical Center
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital d/b/a Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Urology
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute
state: West Virginia
Study officials:
References: