A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
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|ClinicalTrials.gov Identifier: NCT03474107|
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : January 16, 2019
The purpose of this study is to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy.
This study will also compare progression-free survival on study therapy (PFS1); the overall response rate (ORR) and the disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of participants treated with EV to participants treated with chemotherapy.
In addition, this study will evaluate the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy and assess the safety and tolerability of EV, as well as, the quality of life (QOL) and Patient Reported Outcomes (PRO) parameters.
|Condition or disease||Intervention/treatment||Phase|
|Ureteral Cancer Urothelial Cancer Bladder Cancer||Drug: enfortumab vedotin Drug: docetaxel Drug: vinflunine Drug: paclitaxel||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||550 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)|
|Actual Study Start Date :||June 27, 2018|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
Experimental: Arm A: enfortumab vedotin
Participants will receive enfortumab vedotin (EV) on days 1, 8 and 15 of each 28 day cycle.
Drug: enfortumab vedotin
Active Comparator: Arm B: chemotherapy
Participants will receive either docetaxel, vinflunine or paclitaxel as determined prior to participant's randomization. Participants will receive the assigned drug on day 1 of every 21 day cycle.
- Overall Survival (OS) [ Time Frame: Up to 36 months ]OS is defined as the time from randomization to the date of death.
- Progression Free Survival on study therapy (PFS1) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 [ Time Frame: Up to 24 months ]PFS1 is defined as the time from the date of randomization until the date of radiological disease progression (per RECIST V1.1), or until death due to any cause.
- Overall Response Rate (ORR) (Complete Response (CR) and Partial Response(PR)) per RECIST V1.1 [ Time Frame: Up to 24 months ]The ORR is defined as the proportion of participants with a complete or partial objective response based on the RECIST V1.1.
- Disease Control Rate (DCR) (CR + PR + stable disease [SD]) per RECIST V1.1 [ Time Frame: Up to 24 months ]The DCR is defined as the proportion of participants with a complete or partial objective response or a stable disease based on RECIST V1.1.
- Duration of Response (DOR) per RECIST V1.1 [ Time Frame: Up to 24 months ]DOR is defined as the time from the date of the first response CR/PR per RECIST V1.1 (whichever is first recorded) to the date of radiological progression or date of death for participants who achieved CR or PR.
- Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 25 months ]
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).
Treatment Emergent Adverse Event (TEAE) is defined as an adverse event observed or worsened after starting administration of the study drug. The number and percentage of participants with treatment-emergent AEs, Serious Adverse Events (SAEs), AEs leading to withdrawal of treatment, and AEs related to study drug will be summarized by system organ class, preferred term and treatment group. The number and percentage of AEs by severity will also be summarized. All AEs will be listed. A study drug-related TEAE is defined as any TEAE with a causal relationship of YES by the investigator.
- Number of participants with laboratory value abnormalities and/or adverse events [ Time Frame: Up to 24 months ]Number of participants with potentially clinically significant laboratory values.
- Number of participants with vital signs abnormalities and/or adverse events [ Time Frame: Up to 25 months ]Number of participants with potentially clinically significant vital sign values.
- Safety assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to 24 months ]
A standard 12-lead ECG will be performed and assessed using local standard procedures. Clinically significant abnormal findings at screening should be recorded as medical history.
Any abnormal ECGs, including those that worsen from baseline, that is considered to be clinically significant and not related to underlying disease, is to be reported as an (S)AE.
- Safety assessed by Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Up to 25 months ]Summary statistics (number and percent of participants) for each category of the ECOG PS at each assessment will be provided. The change from baseline to final visit or early termination will also be summarized. Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
- Patient reported outcome assessed by quality of life: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Up to 25 months ]The QLQ-C30 was developed to measure aspects of Quality of Life (QoL) pertinent to participants with a broad range of cancers who are participating in clinical trials. The current version of the core instrument (QLQ-C30, Version 3) is a 30-item questionnaire consisting of the following: functional domains (physical, role, cognitive, emotional, social); 3 symptom scales (fatigue, pain, nausea & vomiting); single items for symptoms (shortness of breath, loss of appetite, sleep disturbance, constipation, diarrhea) and financial impact of the disease; and 2 global items (health, overall QoL). Questions 1-28 range from 1 (not at all) to 4 (very much); questions 29-30 range from 1 (very poor) to 7 (excellent).
- Patient reported outcome assessed by quality of life: EuroQOL 5-dimensions (EQ-5D -5L) questionnaire [ Time Frame: Up to 25 months ]The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
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): NCT03474107
|Contact: Astellas Pharma Global Developmentfirstname.lastname@example.org|
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|Study Director:||Senior Medical Director||Astellas Pharma Global Development, Inc.|