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You may be eligible to participate in a carcinoma, transitional cell clinical trial.
Have you or your loved ones been diagnosed with carcinoma, transitional cell? You may be eligible to participate in a carcinoma, transitional cell clinical trial.
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Carcinoma, Transitional Cell Clinical Trial in Orange CA
Have you or your loved ones been diagnosed with carcinoma, transitional cell?
You may be eligible to participate in a carcinoma, transitional cell clinical trial.
Have you or your loved ones been diagnosed with carcinoma, transitional cell? You may be eligible to participate in a carcinoma, transitional cell clinical trial.
Active not recruiting
Male & Female
18 Years +
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body. This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer. This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect. Patients who sign up for this trial must also fall into one of these categories: - Patients have already received treatment with platinum-containing chemotherapy - Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.
Details for the study
Brief Title
A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Official Title
A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy
Brief Summary
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients <br /> with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of <br /> the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other <br /> areas of the body. <br /> <br /> This clinical trial will enroll patients who were previously treated with a kind of <br /> anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for <br /> the treatment of urothelial cancer. <br /> <br /> This study will test if the cancer shrinks with treatment. This study will also look at the <br /> side effects of the drug. A side effect is a response to a drug that is not part of the <br /> treatment effect. <br /> <br /> Patients who sign up for this trial must also fall into one of these categories: <br /> <br /> - Patients have already received treatment with platinum-containing chemotherapy <br /> <br /> - Patients have never received platinum-containing treatment and are not eligible for <br /> treatment with cisplatin.
Detailed Description
Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin
(Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post
marketing study in Japan.
This study will examine the safety and anticancer activity of enfortumab vedotin given
intravenously to patients with locally advanced or metastatic urothelial cancer who
previously received a CPI and either previously received platinum-containing chemotherapy
(Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received
platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of
completion will be considered platinum-naïve. Approximately 100 patients are expected to be
enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of
enfortumab vedotin.
Treatments and/or Procedures
Enfortumab vedotin
Intravenous (IV) infusion on days 1, 8 and 15 every 28 days
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is defined as a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Secondary
Number of Participants With Adverse Events (AEs) at Time of Primary Analysis
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion.
Secondary
PK Parameter for Total Antibody (TAb): Cmax (Serum)
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Secondary
PK Parameter for Free MMAE: AUC (Plasma)
AUC was derived from the PK blood samples collected.
Secondary
PK Parameter for Free MMAE: Tmax (Plasma)
Tmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Secondary
PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Secondary
PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)
AUC was derived from the PK blood samples collected.
Secondary
PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Secondary
PK Parameter for TAb: Tmax (Serum)
Tmax was derived from the PK blood samples collected. Time of maximum concentration corresponds to the end of infusion sample time. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Secondary
Incidence of Antitherapeutic Antibody (ATA)
Participants who were tested positive for ATA at any time post-baseline were considered to be transiently positive or persistently positive if >=2 consecutive samples were confirmed as positive.
Secondary
Duration of Objective Response (DOR) Per BICR
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions is also considered progression. DOR was analyzed using Kaplan-Meier methodology.
Secondary
Progression-Free Survival (PFS) Per BICR
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint.
Secondary
ORR Per Investigator Assessment
The percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR and PR are defined in the ORR per BICR endpoint.
Secondary
DOR Per Investigator Assessment
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or to death due to any cause, whichever comes first. CR and PR are defined in ORR per BICR endpoint. PD is defined in the DOR per BICR endpoint.
Secondary
PFS Per Investigator Assessment
The time from start of study treatment to first documentation of objective tumor progression (PD per RECIST 1.1), or to death due to any cause, whichever comes first. PD is defined in the DOR per BICR endpoint.
Secondary
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.
Secondary
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)
A treatment-emergent laboratory abnormality is a value increases or decrease by 1 toxicity grade after the first study dose.
Secondary
Disease Control Rate at 16 Weeks (DCR16) Per BICR
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Secondary
DCR16 Per Investigator Assessment
Percentage of participants with CR, PR, or stable disease (SD) at Week 16 visit. CR and PR are defined in ORR per BICR endpoint. SD is defined in DCR16 per BICR endpoint.
Secondary
Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as a newly occurring or worsening AE after the first dose of study treatment and within 30 days after the last dose of study treatment.
Secondary
Overall Survival (OS) at Time of Primary Analysis
OS is defined as the time from first dose of enfortumab vedotin to death from any cause. This data is part of a pre-specified primary analysis. Updated data will be provided in a separate outcome measure upon study completion.
Secondary
PK Parameter for TAb: AUC (Serum)
AUC was derived from the PK blood samples collected.
Secondary
Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)
Cmax was derived from the PK blood samples collected. Day 1 data informed by samples collected on Day 1, Day 3, and Day 8. Day 15 data informed by samples collected on Day 15, Day 17, and Day 22.
Study Criteria
Inclusion Criteria: - Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed). - Metastatic disease or locally advanced disease that is not resectable. - Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible. - Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2). - Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy. - Tumor tissue samples must be available for submission to the sponsor prior to study treatment. - Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1). - An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2. - Anticipated life expectancy of ≥3 months as assessed by the investigator. Exclusion Criteria: - Ongoing sensory or motor neuropathy Grade ≥2. - Active central nervous system (CNS) metastases. - Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis. - Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs). - Uncontrolled tumor-related pain or impending spinal cord compression.