Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Urethral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Ramucirumab

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Ramucirumab (10 milligram/kilogram \[mg/kg\]) intravenously (IV) plus docetaxel (75 milligram/square meter \[mg/m²\]) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Placebo IV plus docetaxel (75 mg/m²) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Placebo

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to evaluate the safety and efficacy of the study drug ramucirumab in combination with docetaxel in participants with urothelial cancer who failed prior platinum-based therapy.

A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therapy

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

PFS defined as time from first day of therapy to first evidence of disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If participant does not have complete baseline disease assessment, then PFS time was censored at date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for participant. If participant is not known to have died or have objective progression as of data inclusion cutoff date for analysis, PFS time was censored at last adequate tumor assessment date.

OS is the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data inclusion cutoff date for a particular analysis, OS was censored for that analysis at the last known alive date prior to the data inclusion cutoff date.

ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 millimeter (mm). Tumor-marker results must have normalized. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Best overall response is classified based on the overall responses assessed by study investigators according to RECIST v1.1.

DCR is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).

Objective response was achieved if they had a best overall response of CR or PR. Target lesions- CR: Disappearance of all lesions; any pathological lymph nodes have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study(the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions - CR: Disappearance of all lesions and normalization of tumour marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s). If a participant was not known to have died or have radiographically documented PD as of the data inclusion cutoff date, DOR was censored at the date of the last adequate tumor assessment.

Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment. Scores for global health status/QoL range from 0 to 100 with; higher scores representing better QoL.

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Participants completed the 5-level (no problem, slight problem, moderate problem, severe problem, and inability or extreme problem), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D health state is defined by combining 1 level from each of the 5 dimensions. Scores range from 0 (death) to 1 (perfect health), but scores \<0 are possible based on the algorithm.

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. A unique EQ-5D health state is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a VAS ranging from 100 (best imaginable health state) to 0 (worst imaginable health state).

Cmax of Ramucirumab at the end of ramucirumab infusion.

Cmin of Ramucirumab following administration every 3 weeks.

Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.

Eli Lilly and Company

All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.

Ramucirumab (10 mg/kg) IV plus docetaxel (75 mg/m²) IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Ramucirumab + Docetaxel

Placebo+Docetaxel

Placebo + Docetaxel

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Romania

Hungary

United States

Japan

Ukraine

United Kingdom

Russia

Spain

Greece

Canada

South Korea

Netherlands

Turkey

Belgium

Taiwan

Denmark

Poland

Italy

Mexico

Israel

Australia

France

Germany

Region of Enrollment

Chief Medical Officer

The first randomized participants. Censored participants: Ramucirumab + Docetaxel = 58, Placebo + Docetaxel =38.

Progression Free Survival (PFS)

Ramucirumab (10 mg/kg) IV plus docetaxel IV on day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

All randomized participants. Censored participants: Ramucirumab + Docetaxel = 78, Placebo + Docetaxel = 67.

Overall Survival (OS)

Percentage of Participants With an Objective Response Rate (ORR)

Percentage of Participants With Disease Control Rate (DCR)

All randomized participants with CR or PR. Participants censored in Ramucirumab + Docetaxel = 12 and in Placebo + Docetaxel = 5.

Duration of Response (DoR)

All randomized participants. Censored participants: Ramucirumab + Docetaxel = 160, Placebo + Docetaxel = 173.

Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale

All randomized participants with baseline and 30-day follow-up data.

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score

Placebo IV plus docetaxel (75 mg/m²) IV ion day 1 of each 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)

Cycle 1

Cycle 9

All randomized participants who had evaluable PK data.

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab

Cycle 2

Cycle 3

Cycle 5

PK: Minimum Concentration (Cmin) of Ramucirumab

All randomized participants who received at least one dose of study drug at baseline and post-baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer	NCT02426125	Urothelial Carc...	Ramucirumab Docetaxel Placebo	18 Years -	Eli Lilly and Company
A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer	NCT02426125	Urothelial Carc...	Ramucirumab Docetaxel Placebo	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for carcinoma of the urethra