Safety and Tolerability of TAR-200 and Nivolumab in Subjects With Muscle-Invasive Bladder Cancer

NCT03518320 | Terminated Phase 1 FDA Drug

• 1 other identifier: TAR-200-104
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 6

Brief 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 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; Bladder Cancer TNM Staging Regional Lymph Node (N) N0; Bladder Cancer TNM Staging Regional Lymph Node (N) N1; Bladder Cancer TNM Staging Distant Metastasis (M) M0

Keywords

Bladder Cancer; Urothelial Carcinoma; Cystectomy; Radical Cystectomy

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Study Day 0 to Study Day 180

Study Arms (1)

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.

Drug: Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200; Drug: Nivolumab Injection [Opdivo]

Interventions

Gemcitabine-Releasing Intravesical System (GemRIS)/TAR-200 DRUG

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

TAR-200 and Nivolumab Combination

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

TAR-200 and Nivolumab Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.
• 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.
• 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).

Sponsors & Collaborators

• Taris Biomedical LLC: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

DuPage Medical Group

Hinsdale, Illinois, 60521, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The University of Oklahoma Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christopher Cutie, MD

  Taris Biomedical LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2018
• First Posted: May 8, 2018
• Study Start: January 2, 2019
• Primary Completion: December 11, 2019
• Study Completion: December 11, 2019
• Last Updated: August 27, 2024

Record last verified: 2024-08

Locations

US (6)