Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC
- Conditions
- Non-muscle Invasive Bladder Cancer (NMIBC)
- Interventions
- Registration Number
- NCT03719300
- Lead Sponsor
- Anchiano Therapeutics Israel Ltd.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 32
-
Male or female patients ≥18 years of age at the time of consent
-
Patient must have been adequately treated with BCG defined as at least one of the following (FDA 2018):
- At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy
- At least five of six doses of an initial induction course plus at least two of six doses of a second induction course
- A single course of induction BCG can qualify if the patient has T1 high-grade disease at first evaluation (see 3c)
-
Patient must be BCG-unresponsive defined as at least one of the following (FDA 2018):
- 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.
- 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.
- T1 high-grade disease at the first evaluation following a single course of induction BCG qualifies (Lerner et al. 2015, Steinberg et al. 2016)
-
Patient must have, at study entry, NMIBC indicated by 1 or more of the following:
- Ta or T1 high-grade disease
- CIS disease
-
Patient must have no known evidence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra within 6 months of enrollment
-
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
-
Patient must have adequate hematologic function, as demonstrated by the following:
- Hemoglobin level ≥10 g/dL
- Absolute neutrophil count ≥1.5 x 109/L
- Platelet count ≥100 x 109/L
-
Patient must have adequate liver and renal function as demonstrated by the following:
- Aspartate aminotransferase and alanine aminotransferase each ≤3.0 x upper limit of normal
- 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
- Serum creatinine ≤1.5 x upper limit of normal or measured or calculated creatinine clearance ≥30 mL/min
-
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
-
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
- Patient has current or previous evidence of muscle invasive (muscularis propria) or metastatic bladder cancer disease
- Patient has received prior investigational therapy for NMIBC
- 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
- Patient is intolerant to previous BCG treatment in the absence of meeting other criteria for BCG unresponsiveness and adequate BCG therapy
- Patient has received external beam radiation therapy for bladder cancer at any time or for any other condition
- Patient has an active infection, including urinary tract infection (viral, bacterial, or fungal) and cystitis
- Patient has urinary tract signs or symptoms that preclude retention of drug in the bladder; this does not include anticholinergic drugs
- 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
- Patient is female and is pregnant or breastfeeding
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single Arm BC-819 inodiftagene vixteplasmid inodiftagene vixteplasmid
- Primary Outcome Measures
Name Time Method The Percentage of Patients With Baseline CIS That Achieve a Complete Response After Treatment With BC-819 (Measured at 12 Weeks) 12 weeks Complete response is defined as at least one of the following:
* Negative cystoscopy and negative (including atypical) urine cytology
* Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
* Negative cystoscopy with malignant urine cytology if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative
The complete response in patients with CIS for this endpoint was documented on or after the Week 12 response assessment and on or prior to the Week 48 assessment. Duration of complete response in patients with CIS was calculated from the documented onset of the complete response to the assessment where the patient no longer met the definition of complete response.
- Secondary Outcome Measures
Name Time Method Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 48 Weeks (Overall Population and Subgroup of Patients With CIS) 48 weeks Time to recurrence (Kaplan-Meier plot) recurrence is defined as the reappearance or persistence of high-grade disease, or new high-grade disease. Recurrence must be biopsy proven. Persistence, appearance, or presence of lower grade disease was not considered to be a recurrence event
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) 12, 24, 36, 72, and 96 weeks Time to recurrence (Kaplan-Meier plot) recurrence is defined as the reappearance or persistence of high-grade disease, or new high-grade disease. Recurrence must be biopsy proven. Persistence, appearance, or presence of lower grade disease was not considered to be a recurrence event.
Percentage of Patients Who Are Progression-free at 48, 72, and 96 Weeks 48, 72, and 96 weeks The incidence of PFS at 48, 72, and 96 weeks as well as time to progression estimated using Kaplan-Meir methods. Progression is defined as the development of T2 or greater disease. Sensitivity analyses was performed and included any of the following as progressions:
* An increase in stage from Ta or CIS to T1, or
* Development of T2 or greater, or
* Lymph node disease, or
* Distant metastasisOverall Survival of Patients Enrolled in the Study at 48, 72, and 96 Weeks 48, 72, and 96 weeks Overall survival of patients enrolled in the study at 48, 72, and 96 weeks and survival time was estimated using Kaplan-Meier methods
Quality of Life in Patients Treated With BC-819 48, 72, and 96 weeks Measured by the The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30), a general questionnaire for assessing quality of life in cancer patients, and the Non-Muscle Invasive Bladder Cancer Questionnaire (QLQ-NMIBC24 ) for patients with NBIMC disease. EORTC QLQ-C30 include five functional scales , three symptom scales, a global health status/quality of life scale, and six single items. QLQ-NMIBC24 include five multi-item symptom scales, one multi-item functional scale, and five single-item measures.These scales range in score 0-100 scale and an for functional scales, a higher a higher score corresponds to greater function or quality of life. For symptom scales, a higher score corresponds to greater symptom burden.
Assessment of Safety 9 months The safety was evaluated by assessment of AEs according to CTCAE version 5.0, regardless of relationship to study medication.
Time to Recurrence (Kaplan-Meier Plot) 12, 24, 36, 72, and 96 weeks Time to recurrence (Kaplan-Meier plot) recurrence is defined as the reappearance or persistence of high-grade disease, or new high-grade disease. Recurrence must be biopsy proven. Persistence, appearance, or presence of lower grade disease was not considered to be a recurrence event
Trial Locations
- Locations (48)
American Institute of Research
🇺🇸Los Angeles, California, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Idaho Urologic Institute, PA
🇺🇸Meridian, Idaho, United States
The Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Weill Cornell Medical College - NY Presbyterian Hospital
🇺🇸New York, New York, United States
Albany Medical College
🇺🇸Albany, New York, United States
Alliance Urology Specialists, PA
🇺🇸Greensboro, North Carolina, United States
Spectrum Health Medical Group
🇺🇸Grand Rapids, Michigan, United States
University of Toledo, Dept. of Urology and Kidney Transplant
🇺🇸Toledo, Ohio, United States
MD Anderson Cancer Center at Cooper
🇺🇸Voorhees, New Jersey, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
New Jersey Urology, LLC
🇺🇸Belleville, New Jersey, United States
Urology of Virginia
🇺🇸Virginia Beach, Virginia, United States
West Virginia University Cancer Institute
🇺🇸Morgantown, West Virginia, United States
MidLantic Urology
🇺🇸Bala-Cynwyd, Pennsylvania, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Wichita Urology Group
🇺🇸Wichita, Kansas, United States
Baylor College of Medicine Medical Center
🇺🇸Houston, Texas, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
The Urology Center of Colorado
🇺🇸Denver, Colorado, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Urology Associates, P.C.
🇺🇸Nashville, Tennessee, United States
Alaska Urological Institute
🇺🇸Anchorage, Alaska, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Urological Associates of Southern Arizona
🇺🇸Tucson, Arizona, United States
Arkansas Urology
🇺🇸Little Rock, Arkansas, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University of Florida Health Jacksonville, Shands Hospital
🇺🇸Jacksonville, Florida, United States
North Idaho Urology
🇺🇸Coeur d'Alene, Idaho, United States
University of Illinois Hospital and Health Systems (Outpatient Care Center)
🇺🇸Chicago, Illinois, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Johns Hopkins Medical Institution
🇺🇸Baltimore, Maryland, United States
Duke University
🇺🇸Durham, North Carolina, United States
Carolina Urology Partners, PLLC
🇺🇸Huntersville, North Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Regional Urology
🇺🇸Greenville, South Carolina, 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
Michigan Institute of Urology, PC
🇺🇸Troy, Michigan, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Ochsner Clinical Foundation
🇺🇸New Orleans, Louisiana, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
UNC Chapel Hill Hospital, Urology Clinic
🇺🇸Chapel Hill, North Carolina, United States
Medical University South Carolina
🇺🇸Charleston, South Carolina, United States
Virginia Urology
🇺🇸Richmond, Virginia, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States