Non-muscle Invasive Bladder Cancer (NMIBC)Phase 2NCT03719300
Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC
A Phase 2 study testing inodiftagene vixteplasmid in people with Non-muscle Invasive Bladder Cancer (NMIBC), run by Anchiano Therapeutics Israel Ltd. at 48 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-muscle Invasive Bladder Cancer (NMIBC)
- What is being tested?
- inodiftagene vixteplasmid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 48 sitesUnited States
- Study dates
- 20 Mar 2019to 18 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
Show all 24Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
48 sites in 1 country.
48 sites in 1 country
United States48 sites
Albany Medical College
Albany, New York, 12208
Alaska Urological Institute
Anchorage, Alaska, 99503
Emory University
Atlanta, Georgia, 30322
MidLantic Urology
Bala-Cynwyd, Pennsylvania, 19004
Johns Hopkins Medical Institution
Baltimore, Maryland, 21287
New Jersey Urology, LLC
Belleville, New Jersey, 08043
UNC Chapel Hill Hospital, Urology Clinic
Chapel Hill, North Carolina, 27514
Medical University South Carolina
Charleston, South Carolina, 29425
University of Illinois Hospital and Health Systems (Outpatient Care Center)
Chicago, Illinois, 60612
North Idaho Urology
Coeur d'Alene, Idaho, 83814
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
The Urology Center of Colorado
Denver, Colorado, 80211
Duke University
Durham, North Carolina, 27710
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Spectrum Health Medical Group
Grand Rapids, Michigan, 49546
Alliance Urology Specialists, PA
Greensboro, North Carolina, 27403
Regional Urology
Greenville, South Carolina, 29605
Baylor College of Medicine Medical Center
Houston, Texas, 77030
The Methodist Hospital d/b/a Houston Methodist Hospital
Houston, Texas, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Carolina Urology Partners, PLLC
Huntersville, North Carolina, 28078
Mayo Clinic Florida
Jacksonville, Florida, 32224
University of Florida Health Jacksonville, Shands Hospital
Jacksonville, Florida, 33209
Arkansas Urology
Little Rock, Arkansas, 72211
American Institute of Research
Los Angeles, California, 90017
Idaho Urologic Institute, PA
Meridian, Idaho, 83642
West Virginia University Cancer Institute
Morgantown, West Virginia, 26506
Urology Associates, P.C.
Nashville, Tennessee, 37209
Tulane University School of Medicine
New Orleans, Louisiana, 70114
Ochsner Clinical Foundation
New Orleans, Louisiana, 70121
Weill Cornell Medical College - NY Presbyterian Hospital
New York, New York, 10065
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Virginia Urology
Richmond, Virginia, 23235
Mayo Clinic
Rochester, Minnesota, 55905
UC Davis Medical Center
Sacramento, California, 95817
Saint Louis University
St Louis, Missouri, 63110
Washington University
St Louis, Missouri, 63110
SUNY Upstate Medical University
Syracuse, New York, 13210
Montefiore Medical Center
The Bronx, New York, 10461
University of Toledo, Dept. of Urology and Kidney Transplant
Toledo, Ohio, 43614
Michigan Institute of Urology, PC
Troy, Michigan, 48084
Urological Associates of Southern Arizona
Tucson, Arizona, 85715
Urology of Virginia
Virginia Beach, Virginia, 23462
MD Anderson Cancer Center at Cooper
Voorhees Township, New Jersey, 08103
The University of Kansas Cancer Center
Westwood, Kansas, 66205
Wichita Urology Group
Wichita, Kansas, 67226
About this study
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
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.
Read the 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.
- Being tested
- inodiftagene vixteplasmid
- Keywords
- BCG-unresponsive
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inodiftagene vixteplasmidDrug
Also called BC-819
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
| Study group | Role | What they receive |
|---|---|---|
| Single Arm BC-819 | Experimental | inodiftagene vixteplasmid Receives: Drug: inodiftagene vixteplasmid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (7)
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
Measured: 48 weeks
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.
Measured: 12, 24, 36, 72, and 96 weeks
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
Measured: 48, 72, and 96 weeks
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
Measured: 48, 72, and 96 weeks
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.
Measured: 48, 72, and 96 weeks
Assessment of Safety
The safety was evaluated by assessment of AEs according to CTCAE version 5.0, regardless of relationship to study medication.
Measured: 9 months
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
Measured: 12, 24, 36, 72, and 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start20 Mar 2019
- Primary completion18 Nov 2019
- Study completion18 Dec 2019
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-muscle Invasive Bladder Cancer (NMIBC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anchiano Therapeutics Israel Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03719300
- Sponsor's protocol ID
- BC-819-18-204
- Status last verified
- Aug 2020
- First submitted
- 18 Oct 2018
- Last updated
- 19 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03719300
- Acronym / sponsor ID
- BC-819-18-204
- Keywords
- BCG-unresponsive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Anchiano Therapeutics Israel Ltd.Industry (pharma, biotech, devices)
- Study start
- 20 Mar 2019 (actual)
- Primary completion
- 18 Nov 2019 (actual)
- Study completion
- 18 Dec 2019 (actual)
- First posted
- 25 Oct 2018 (actual)
- Results
- Posted 19 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm BC-819 | Experimental | Drug: inodiftagene vixteplasmidinodiftagene vixteplasmid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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):
- Patient must be BCG-unresponsive defined as at least one of the following (FDA 2018):
- Patient must have, at study entry, NMIBC indicated by 1 or more of the following:
- Patient must have no known evidence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra within 6 months of enrollment
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inodiftagene vixteplasmidAlso: BC-819BC-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 | Drug | Single Arm BC-819 |
Primary outcome
The Percentage of Patients With Baseline CIS That Achieve a Complete Response After Treatment With BC-819 (Measured at 12 Weeks)
Time frame: 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.
7 secondary outcomes
Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 48 Weeks (Overall Population and Subgroup of Patients With CIS)
Time frame: 48 weeks
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 frame: 12, 24, 36, 72, and 96 weeks
Percentage of Patients Who Are Progression-free at 48, 72, and 96 Weeks
Time frame: 48, 72, and 96 weeks
Overall Survival of Patients Enrolled in the Study at 48, 72, and 96 Weeks
Time frame: 48, 72, and 96 weeks
Quality of Life in Patients Treated With BC-819
Time frame: 48, 72, and 96 weeks
Assessment of Safety
Time frame: 9 months
Time to Recurrence (Kaplan-Meier Plot)
Time frame: 12, 24, 36, 72, and 96 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
48 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing inodiftagene vixteplasmid in people with Non-muscle Invasive Bladder Cancer (NMIBC), run by Anchiano Therapeutics Israel Ltd. at 48 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Percentage of Patients With Baseline CIS That Achieve a Complete Response After Treatment With BC-819 (Measured at 12 Weeks) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2020.