Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC

NCT ID: NCT03719300

Last Updated: 2020-08-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-20
• Study Completion Date: 2019-12-18

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.

Conditions

Non-muscle Invasive Bladder Cancer (NMIBC)

Study Design

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

Study Groups

Single Arm BC-819

inodiftagene vixteplasmid

Group Type: EXPERIMENTAL

inodiftagene vixteplasmid

Intervention Type: DRUG

BC-819 at 20 mg/50 mL, instilled intravesically into the bladder, with a retention time of at least 30 minutes (up to 2 hours).

Induction Phase (weekly treatments): 10 weekly treatments; Maintenance Phase: treatment every 3 weeks for up to 84 additional weeks

Interventions

inodiftagene vixteplasmid

BC-819 at 20 mg/50 mL, instilled intravesically into the bladder, with a retention time of at least 30 minutes (up to 2 hours).

Induction Phase (weekly treatments): 10 weekly treatments; Maintenance Phase: treatment every 3 weeks for up to 84 additional weeks

Intervention Type: DRUG

Other Intervention Names

BC-819

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

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

Sponsors

Anchiano Therapeutics Israel Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Alaska Urological Institute

Anchorage, Alaska, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

Urological Associates of Southern Arizona

Tucson, Arizona, United States

Arkansas Urology

Little Rock, Arkansas, United States

American Institute of Research

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

University of Florida Health Jacksonville, Shands Hospital

Jacksonville, Florida, United States

Emory University

Atlanta, Georgia, United States

North Idaho Urology

Coeur d'Alene, Idaho, United States

Idaho Urologic Institute, PA

Meridian, Idaho, United States

University of Illinois Hospital and Health Systems (Outpatient Care Center)

Chicago, Illinois, United States

The University of Kansas Cancer Center

Westwood, Kansas, United States

Wichita Urology Group

Wichita, Kansas, United States

Tulane University School of Medicine

New Orleans, Louisiana, United States

Ochsner Clinical Foundation

New Orleans, Louisiana, United States

Johns Hopkins Medical Institution

Baltimore, Maryland, United States

Spectrum Health Medical Group

Grand Rapids, Michigan, United States

Michigan Institute of Urology, PC

Troy, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Saint Louis University

St Louis, Missouri, United States

Washington University

St Louis, Missouri, United States

New Jersey Urology, LLC

Belleville, New Jersey, United States

MD Anderson Cancer Center at Cooper

Voorhees Township, New Jersey, United States

Albany Medical College

Albany, New York, United States

Weill Cornell Medical College - NY Presbyterian Hospital

New York, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

UNC Chapel Hill Hospital, Urology Clinic

Chapel Hill, North Carolina, United States

Duke University

Durham, North Carolina, United States

Alliance Urology Specialists, PA

Greensboro, North Carolina, United States

Carolina Urology Partners, PLLC

Huntersville, North Carolina, United States

University of Toledo, Dept. of Urology and Kidney Transplant

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University South Carolina

Charleston, South Carolina, United States

Regional Urology

Greenville, South Carolina, United States

Urology Associates, P.C.

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine Medical Center

Houston, Texas, United States

The Methodist Hospital d/b/a Houston Methodist Hospital

Houston, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Virginia Urology

Richmond, Virginia, United States

Urology of Virginia

Virginia Beach, Virginia, United States

West Virginia University Cancer Institute

Morgantown, West Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BC-819-18-204

Identifier Type: -

Identifier Source: org_study_id