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A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guerin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

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ClinicalTrials.gov Identifier: NCT04640623
Recruitment Status : Recruiting
First Posted : November 23, 2020
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease.

Condition or disease Intervention/treatment Phase
Urinary Bladder Neoplasms Drug: TAR-200 Drug: Cetrelimab Phase 2

Detailed Description:
Bladder cancer is the tenth most common malignancy worldwide. The natural history of high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) is unpredictable; rates of recurrence vary from 15 percent (%) to 78%, and rates of progression to muscle invasion and metastasis vary from less than (<) 1 to 45%. The TAR-200/gemcitabine (JNJ-17000139-AAC) product (hereafter, TAR-200) is an intravesical drug delivery system regulated as an investigational drug. The drug constituent consists of gemcitabine minitablets, and osmotic minitablets containing urea as the osmotic agent. Cetrelimab (JNJ-63723283) is a fully human immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds PD-1. This study consists 3 periods: screening phase (up to 30 days); treatment phase (up to 2 years); follow up phase (up to 5 years). Total duration of study is up to 5 years. Efficacy, safety, pharmacokinetics (PK), and biomarkers will be assessed at specified time points during this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2b Clinical Study Evaluating Efficacy and Safety of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guerin (BCG) Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy
Actual Study Start Date : December 18, 2020
Estimated Primary Completion Date : October 24, 2024
Estimated Study Completion Date : July 27, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: Cohort 1: TAR-200 and Cetrelimab
TAR-200 is placed into the bladder through an inserter on Day 0 and will be dosed every 21 days for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Study Year 2). In addition, Cetrelimab will be administered.
Drug: TAR-200
TAR-200 will be administered transuretherally.
Other Names:
  • JNJ-17000139
  • Gemcitabine-Releasing Intravesical System

Drug: Cetrelimab
Cetrelimab will be administered.
Other Name: JNJ-63723283

Experimental: Cohort 2: TAR-200
TAR-200 is placed into the bladder through an inserter on Day 0 and will be dosed every 21 days for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Study Year 2).
Drug: TAR-200
TAR-200 will be administered transuretherally.
Other Names:
  • JNJ-17000139
  • Gemcitabine-Releasing Intravesical System

Experimental: Cohort 3: Cetrelimab
Participants will receive Cetrelimab.
Drug: Cetrelimab
Cetrelimab will be administered.
Other Name: JNJ-63723283




Primary Outcome Measures :
  1. Overall Clinical Response (CR) Rate [ Time Frame: Up to 5 years ]
    Overall CR rate, is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.


Secondary Outcome Measures :
  1. Durability of Response (DOR) [ Time Frame: Up to 5 years ]
    DOR is defined from the time of first CR achieved to first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR.

  2. Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS, defined as the time from first dose of study treatment to death; if a participant has not died at the time of analysis, the participant will be censored at the date last known alive.

  3. Cohort 1 and 2: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma [ Time Frame: Up to Week 21 ]
    Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed.

  4. Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies [ Time Frame: Predose, up to 3 years ]
    Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis.

  5. Number of Participants with Anti-cetrelimab Antibodies [ Time Frame: Predose, up to 3 years ]
    Number of participants with anti-cetrelimab antibodies will be reported.

  6. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores [ Time Frame: Baseline, up to 3 years and 4 months ]
    EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much).

  7. Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores [ Time Frame: Baseline, up to 3 years and 4 months ]
    EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much).

  8. Number of Participants with Adverse Events (AEs) by Severity Grades [ Time Frame: Up to 5 years ]
    An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity grades ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

  9. Number of Product Quality Complaints (PQC) [ Time Frame: Up to 3 years and 1 month ]
    A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or packaging, that is, any dissatisfaction relative to the identity, quality, durability, reliability, or performance of a distributed product, including its labeling, drug delivery system, or package integrity.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of high-risk, non-muscle invasive urothelial carcinoma in situ (CIS; Tis), with or without papillary disease (T1, high-grade Ta) within 12 months of completion of adequate Bacillus Calmette-Guerin (BCG) therapy. Mixed histology tumours are allowed if urothelial differentiation (transitional cell histology) is predominant (example, less than (<) 20 percent (%) variant histologic subtype). However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. For participants with lamina propria invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor (TURBT), muscularis propria must be present in order to rule out Muscle Invasive Bladder Cancer (MIBC)
  • Visible papillary disease must be fully resected (absent) prior to randomization (residual CIS acceptable) and documented at screening cystoscopy
  • Participants must be ineligible for or have elected not to undergo radical cystectomy
  • BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or 2 of 6 doses of a second induction course
  • Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2

Exclusion Criteria:

  • Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV
  • Concurrent extra-vesical (that is, urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
  • Participants with an active, known or suspected autoimmune disease. Participants with autoimmune disorders not requiring systemic treatment (example, skin conditions such as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll
  • Known active hepatitis B or C infection (for example, participants with history of hepatitis C infection but normal hepatitis C virus polymerase chain reaction test and participants with hepatitis B with positive hepatitis B surface antigen (HBsAg) antibody are allowed)
  • Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04640623


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04640623    
Other Study ID Numbers: CR108921
2020-002646-16 ( EudraCT Number )
17000139BLC2001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 23, 2020    Key Record Dates
Last Update Posted: March 29, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs