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

Non-muscle Invasive Bladder Cancer (NMIBC) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03719300
• Other study ID #: BC-819-18-204
• Status: Terminated
• Phase: Phase 2
• Start date: March 20, 2019
• Est. completion date: December 18, 2019

Study information

• Verified date: August 2020
• Source: Anchiano Therapeutics Israel Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: December 18, 2019
• Est. primary completion date: November 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Non-muscle Invasive Bladder Cancer (NMIBC)
• Urinary Bladder Neoplasms

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	Albany Medical College	Albany	New York
United States	Alaska Urological Institute	Anchorage	Alaska
United States	Emory University	Atlanta	Georgia
United States	MidLantic Urology	Bala-Cynwyd	Pennsylvania
United States	Johns Hopkins Medical Institution	Baltimore	Maryland
United States	New Jersey Urology, LLC	Belleville	New Jersey
United States	Montefiore Medical Center	Bronx	New York
United States	UNC Chapel Hill Hospital, Urology Clinic	Chapel Hill	North Carolina
United States	Medical University South Carolina	Charleston	South Carolina
United States	University of Illinois Hospital and Health Systems (Outpatient Care Center)	Chicago	Illinois
United States	North Idaho Urology	Coeur d'Alene	Idaho
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	The Urology Center of Colorado	Denver	Colorado
United States	Duke University	Durham	North Carolina
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Spectrum Health Medical Group	Grand Rapids	Michigan
United States	Alliance Urology Specialists, PA	Greensboro	North Carolina
United States	Regional Urology	Greenville	South Carolina
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	Carolina Urology Partners, PLLC	Huntersville	North Carolina
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	University of Florida Health Jacksonville, Shands Hospital	Jacksonville	Florida
United States	Arkansas Urology	Little Rock	Arkansas
United States	American Institute of Research	Los Angeles	California
United States	Idaho Urologic Institute, PA	Meridian	Idaho
United States	West Virginia University Cancer Institute	Morgantown	West Virginia
United States	Urology Associates, P.C.	Nashville	Tennessee
United States	Ochsner Clinical Foundation	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Weill Cornell Medical College - NY Presbyterian Hospital	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	The Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Virginia Urology	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of Toledo, Dept. of Urology and Kidney Transplant	Toledo	Ohio
United States	Michigan Institute of Urology, PC	Troy	Michigan
United States	Urological Associates of Southern Arizona	Tucson	Arizona
United States	Urology of Virginia	Virginia Beach	Virginia
United States	MD Anderson Cancer Center at Cooper	Voorhees	New Jersey
United States	The University of Kansas Cancer Center	Westwood	Kansas
United States	Wichita Urology Group	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Anchiano Therapeutics Israel Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Patients With Baseline CIS That Achieve a Complete Response After Treatment With BC-819 (Measured at 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.	12 weeks
Secondary	Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 48 Weeks (Overall Population and Subgroup of Patients With CIS)	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	48 weeks
Secondary	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)	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.	12, 24, 36, 72, and 96 weeks
Secondary	Percentage of Patients Who Are Progression-free at 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 metastasis	48, 72, and 96 weeks
Secondary	Overall Survival of Patients Enrolled in the Study at 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	48, 72, and 96 weeks
Secondary	Quality of Life in Patients Treated With BC-819	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.	48, 72, and 96 weeks
Secondary	Assessment of Safety	The safety was evaluated by assessment of AEs according to CTCAE version 5.0, regardless of relationship to study medication.	9 months
Secondary	Time to Recurrence (Kaplan-Meier Plot)	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	12, 24, 36, 72, and 96 weeks