Bladder Cancer TNM Staging Primary Tumor (T) T2Phase 1NCT03518320
Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer
A Phase 1 study testing Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 and Nivolumab Injection [Opdivo] in people with Bladder Cancer TNM Staging Primary Tumor (T) T2 and Bladder Cancer TNM Staging Primary Tumor (T) T2A, run by Taris Biomedical LLC at 6 sites in United States.
Trial summary
The purpose of this study is to determine if TAR-200, an investigational drug delivery system, in combination with nivolumab is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) during an 84-day dosing cycle induction period comprised of four… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B
- What is being tested?
- Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 and Nivolumab Injection [Opdivo]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 6 sitesUnited States
- Study dates
- 2 Jan 2019to 11 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed.
- Subjects with a total tumor size of ≤2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ≤2 cm to be eligible for treatment.
- Adequate bone marrow, liver, and renal function, as documented by the following laboratory assessments conducted within 28 days prior to dosing:
- Hemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC) ≥1,500/mm3
- Platelet count ≥100,000/mm3
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- Total bilirubin ≤1.5x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN
- Glomerular filtration rate (GFR) ≥30 ml/min/1.73 m2 (assessed using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation)
- Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination.
- Deemed eligible for and willing to undergo RC by the attending urologist.
- Subjects must refuse cisplatin-based combination chemotherapy (and understand the risk and benefits of doing so) or be deemed ineligible for cisplatin-based chemotherapy by meeting at least one of the following criteria:
- GFR <60 mL/min/1.73 m2 (assessed using the CKD-EPI equation)
- Common Terminology Criteria for Adverse Events (CTCAE) v4 Grade ≥2 audiometric hearing loss
- CTCAE v4 Grade ≥2 peripheral neuropathy
- Prior systemic chemotherapy for indications other than urothelial cell carcinoma of the bladder is permitted. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (National Cancer Institute CTCAE version 4.03) or baseline before administration of study drug. Participants with toxicities attributed to prior anti cancer therapy which are not expected to resolve and result in long lasting sequelae, such as peripheral neuropathy after platinum-based therapy or audiometric hearing loss, are permitted to enroll.
- Written informed consent and authorization for release of personal health information obtained according to local laws.
- Age ≥18 years at the time of consent.
- Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception (hormonal or intrauterine device [IUD] method of birth control with a failure rate of <1% when used consistently and correctly; or abstinence) for the duration of treatment with TAR-200 in combination with nivolumab plus 5 half-lives of study treatment, plus 30 days (duration of ovulatory cycle), for a total of 5 months post treatment completion. Note: WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this protocol.
- WOCBP must have a negative pregnancy test within 24 hours prior to Study Day 0.
- Males must be willing to use an effective method of contraception to avoid seminal transfer (double barrier method) or abstinence for the duration of treatment with TAR 200 in combination with nivolumab plus 5 half-lives of the study treatment, plus 90 days (duration of sperm turnover), for a total of 7 months post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.
- Azoospermic males should also use double barrier contraceptive methods to avoid contamination of the non-treatment sexual partner.
Who cannot join
- Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome.
- Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
- Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
- Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
- Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
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- Presence of any bladder or urethral anatomic feature that in the opinion of the investigator may prevent the safe placement, indwelling use, or removal of TAR 200.
- Pyeloureteral tube externalized to the skin is exclusionary. Unilateral nephrostomy tube or ureteral stent is permitted as long as it does not interfere with placement or retention of TAR-200 in the bladder.
- Indwelling catheters are not permitted.
- Subjects with evidence of bladder perforation during diagnostic cystoscopy may be treated if perforation has resolved prior to dosing.
- Bladder post-void residual volume of >500 mL.
- History of diagnosis of neurogenic bladder requiring intermittent catheterization.
- Active, uncontrolled urogenital bacterial, viral or fungal infections, including urinary tract infection (UTI). Skin/nail fungal infections are not exclusionary. Subjects with active shingles (varicella zoster infection) will be excluded from the study.
- Subjects with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus RNA or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome. Note: Testing for HIV must be performed at sites where mandated locally.
- Uncontrolled adrenal insufficiency.
- New York Heart Association Functional Classification of Heart Failure: Class III or IV (Appendix 1).
- Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
- Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Subjects must have recovered from the effects of major surgery requiring general anesthetic or significant traumatic injury at least 14 days before Study Day 0.
- History of allergy or hypersensitivity to gemcitabine (or other drug excipients in TAR-200) or drugs chemically-related to gemcitabine.
- History of allergy or hypersensitivity to the device constituent or Inserter materials.
- History of allergy or hypersensitivity to nivolumab drug components.
- Female subject who is pregnant (as verified by urine test at time of screening) or lactating or of childbearing potential and not using acceptable methods of contraception.
- Difficulty providing blood samples.
- Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- Use of an investigational product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Study Day 0.
- Prisoners or subjects who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a subject. Strict conditions apply and sponsor approval is required.)
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
- Other protocol defined inclusion/exclusion criteria could apply.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Duke University Medical Center
Durham, North Carolina, 27710
DuPage Medical Group
Hinsdale, Illinois, 60521
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
The University of Oklahoma Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of Rochester Medical Center
Rochester, New York, 14642
About this study
Official title: A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy
The purpose of this study is to determine if TAR-200, an investigational drug delivery system, in combination with nivolumab is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) during an 84-day dosing cycle induction period comprised of four consecutive 21-day dosing cycles.
- Conditions
- Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B
- Being tested
- Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200, Nivolumab Injection [Opdivo]
- Keywords
- Bladder Cancer, Urothelial Carcinoma, Cystectomy, Radical Cystectomy
- Medical subject headings
- Urinary Bladder Neoplasms, Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200Drug
TAR-200 will be placed in the bladder through an inserter and gradually release gemcitabine for four consecutive 21-day dosing cycles for a total period of approximately 84 days
Nivolumab Injection [Opdivo]Drug
Nivolumab will be given intravenously on specified days for four consecutive 21-day dosing cycles for a total period of approximately 84 days
| Study group | Role | What they receive |
|---|---|---|
| TAR-200 and Nivolumab Combination | Experimental | Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 is placed into the bladder through an Inserter and gradually releases gemcitabine during the 21-day indwelling period before being removed. In combination, subjects are dosed intravenously with a Nivolumab Injection [Opdivo] within 3 days of TAR-200 placement. Subjects will receive four consecutive 21-day dosing cycles of the combination of TAR-200 and Nivolumab prior to radical cystectomy. Receives: Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200; Drug: Nivolumab Injection [Opdivo] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 in combination with Nivolumab as assessed by CTCAE V4.0.
Will be assessed through the duration of the study by reported AEs
Measured: Study Day 0 to Study Day 180
Number of participants that do not require treatment discontinuation prior to the scheduled end date due to meeting any of the Subject Stopping Safety criteria or other drug or device related AE
Will be assessed through the duration of the study by reported treatment discontinuation prior to the scheduled date
Measured: Study Day 0 to Study Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2018
- Study start2 Jan 2019
- Primary completion11 Dec 2019
- Study completion11 Dec 2019
Why it stopped: Business objectives have changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder Cancer TNM Staging Primary Tumor (T) T2Studies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taris Biomedical LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Christopher Cutie, MD, Study director, Taris Biomedical LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03518320
- Sponsor's protocol ID
- TAR-200-104
- Status last verified
- Aug 2024
- First submitted
- 10 Apr 2018
- Last updated
- 27 Aug 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Study of TAR-200 in Combination With Nivolumab (OPDIVO) in Subjects With Muscle-Invasive Urothelial Carcinoma of the Bladder Who Are Scheduled for Radical Cystectomy and Are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT03518320
- Acronym / sponsor ID
- TAR-200-104
- Conditions
- Bladder Cancer TNM Staging Primary Tumor (T) T2, Bladder Cancer TNM Staging Primary Tumor (T) T2A, Bladder Cancer TNM Staging Primary Tumor (T) T2B, Bladder Cancer TNM Staging Primary Tumor (T) T3, Bladder Cancer TNM Staging Primary Tumor (T) T3A, Bladder Cancer TNM Staging Primary Tumor (T) T3B
- Keywords
- Bladder Cancer, Urothelial Carcinoma, Cystectomy, Radical Cystectomy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business objectives have changed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Taris Biomedical LLCIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 2 Jan 2019 (actual)
- Primary completion
- 11 Dec 2019 (actual)
- Study completion
- 11 Dec 2019 (actual)
- First posted
- 8 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if TAR-200, an investigational drug delivery system, in combination with nivolumab is safe and tolerable in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy (RC) during an 84-day dosing cycle induction period comprised of four consecutive 21-day dosing cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TAR-200 and Nivolumab Combination | Experimental | Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200, Drug: Nivolumab Injection [Opdivo]Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 is placed into the bladder through an Inserter and gradually releases gemcitabine during the 21-day indwelling period before being removed. In combination, subjects are dosed intravenously with a Nivolumab Injection [Opdivo] within 3 days of TAR-200 placement. Subjects will receive four consecutive 21-day dosing cycles of the combination of TAR-200 and Nivolumab prior to radical cystectomy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed.
- Subjects with a total tumor size of ≤2 cm following TURBT are eligible. Subjects with a tumor or tumors totaling >2 cm at screening must undergo a second debulking TURBT to reduce the tumor(s) to ≤2 cm to be eligible for treatment.
- Adequate bone marrow, liver, and renal function, as documented by the following laboratory assessments conducted within 28 days prior to dosing:
- Willing to undergo multiple cystoscopies during the study for TAR-200 removal and post-insertion examination.
- Deemed eligible for and willing to undergo RC by the attending urologist.
Key exclusion criteria (32 listed)
- Active malignancies within 3 years except for those with a negligible risk of metastasis or death treated with expected curative outcome.
- Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
- Prior treatment with an anti-programmed death-1 (PD-1), anti-PD-L1, anti PD L2, anti-CD137, or anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co stimulation or checkpoint pathways.
- Pelvic radiotherapy administered within less than 6 months prior to enrollment. Subjects who received radiotherapy ≥6 months prior to enrollment must demonstrate no cystoscopic evidence or symptoms of radiation cystitis.
- Subjects who require immunosuppressive medications such as methotrexate, tumor necrosis factor inhibitors, or systemic corticosteroids (>10 mg/day prednisone equivalents) within 2 weeks prior to study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
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 |
|---|---|---|
| Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200TAR-200 will be placed in the bladder through an inserter and gradually release gemcitabine for four consecutive 21-day dosing cycles for a total period of approximately 84 days | Drug | TAR-200 and Nivolumab Combination |
| Nivolumab Injection [Opdivo]Nivolumab will be given intravenously on specified days for four consecutive 21-day dosing cycles for a total period of approximately 84 days | Drug | TAR-200 and Nivolumab Combination |
Primary outcome
Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 in combination with Nivolumab as assessed by CTCAE V4.0.
Time frame: Study Day 0 to Study Day 180
Will be assessed through the duration of the study by reported AEs
Number of participants that do not require treatment discontinuation prior to the scheduled end date due to meeting any of the Subject Stopping Safety criteria or other drug or device related AE
Time frame: Study Day 0 to Study Day 180
Will be assessed through the duration of the study by reported treatment discontinuation prior to the scheduled date
Results and safety
The study was stopped early (reason given: Business objectives have changed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
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.
Christopher Cutie, MD study director
Taris Biomedical LLC
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 and Nivolumab Injection [Opdivo] in people with Bladder Cancer TNM Staging Primary Tumor (T) T2 and Bladder Cancer TNM Staging Primary Tumor (T) T2A, run by Taris Biomedical LLC at 6 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 22 inclusion and 32 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 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business objectives have changed). Results are not available in the source record.
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?
Number of participants with incidence of treatment emergent adverse events (TEAEs) over 4 consecutive 21-day dosing cycles of TAR-200 in combination with Nivolumab as assessed by CTCAE V4.0. (time frame: Study Day 0 to Study Day 180). The study lists 2 primary outcomes in all. 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 27 Aug 2024.