Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02426125




Registration number
NCT02426125
Ethics application status
Date submitted
21/04/2015
Date registered
24/04/2015
Date last updated
21/08/2023

Titles & IDs
Public title
A Study of Ramucirumab (LY3009806) Plus Docetaxel in Participants With Urothelial Cancer
Scientific title
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
Secondary ID [1] 0 0
I4T-MC-JVDC
Secondary ID [2] 0 0
15679
Universal Trial Number (UTN)
Trial acronym
RANGE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Urothelial Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Bladder - transitional cell cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ramucirumab
Treatment: Drugs - Docetaxel
Treatment: Drugs - Placebo

Experimental: Ramucirumab + Docetaxel - 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 comparator: Placebo + Docetaxel - 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.


Treatment: Drugs: Ramucirumab
Administered IV

Treatment: Drugs: Docetaxel
Administered IV

Treatment: Drugs: Placebo
Administered IV
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Randomization to Radiological Disease Progression or Death from Any Cause (Up to 18 Months)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Randomization to Date of Death from Any Cause (Up to 31.1 Months)
Secondary outcome [2] 0 0
Percentage of Participants With an Objective Response Rate (ORR)
Timepoint [2] 0 0
Randomization to Disease Progression (Up to 29.7 Months)
Secondary outcome [3] 0 0
Percentage of Participants With Disease Control Rate (DCR)
Timepoint [3] 0 0
Randomization to Disease Progression (Up to 29.7 Months)
Secondary outcome [4] 0 0
Duration of Response (DoR)
Timepoint [4] 0 0
Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 28.4 Months)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
Secondary outcome [6] 0 0
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
Timepoint [6] 0 0
Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
Secondary outcome [7] 0 0
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)
Timepoint [7] 0 0
Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
Secondary outcome [8] 0 0
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Timepoint [8] 0 0
Cycle 1 and Cycle 9, Day 1: Predose, Postdose
Secondary outcome [9] 0 0
PK: Minimum Concentration (Cmin) of Ramucirumab
Timepoint [9] 0 0
Day 1 of Cycle 2, 3, 5 and 9 (Predose and Postdose)
Secondary outcome [10] 0 0
Number of Participants With Anti-Ramucirumab Antibodies
Timepoint [10] 0 0
29.7 Months

Eligibility
Key inclusion criteria
* Have histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis.
* Had disease progression while on a platinum containing regimen in the first-line setting or within 14 months after completing the first-line platinum regimen. Participants who received treatment with one immune checkpoint inhibitor regimen are eligible (for example Programmed death 1 (PD-1), Programmed death-ligand 1 (PDL1), or CTLA4) and may have a longer interval since prior platinum-containing therapy (=24 months).
* Have a life expectancy of =3 months.
* Have received no more than one prior systemic chemotherapy regimen in the relapsed or metastatic setting. Prior treatment with no more than one prior immune checkpoint inhibitor is permitted and will not be considered as a line of systemic chemotherapy.
* Have measurable disease or nonmeasurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
* Have an Eastern Cooperative Oncology Group (ECOG) of 0 or 1.
* Have adequate hematologic function.
* Have adequate coagulation function.
* Have adequate hepatic function.
* The participant does not have:

* cirrhosis at a level of Child-Pugh B (or worse)
* cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis
* Have adequate renal function as defined by creatinine clearance >30 milliliters/minute.
* Have urinary protein =1+ on dipstick or routine urinalysis.
* The participant is willing to provide blood, urine, and tissue samples for research purposes.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Have received more than one prior systemic chemotherapy regimen for metastatic disease.
* Have received prior systemic taxane therapy for transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic).
* Have received more than one prior antiangiogenic agent (that is, bevacizumab, sorafenib, sunitinib) for TCC of the urothelium.
* Have received radiation therapy within 4 weeks (=4 weeks) prior to randomization or has not recovered from toxic effects of the treatment that was given >4 weeks prior to randomization.
* Have a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
* Have experienced a Grade =3 bleeding event within 3 months (=3 months) prior to randomization.
* Have uncontrolled intercurrent illness, including, but not limited to symptomatic anemia, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness, or any other serious uncontrolled medical disorders.
* Have experienced any arterial or venothrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 6 months (=6 months) prior to randomization.
* Have known untreated brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease.
* Have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome-related illness.
* Have undergone major surgery within 28 days (=28 days) prior to randomization or subcutaneous venous access device placement within 7 days (=7 days) prior to randomization.
* The participant is pregnant prior to randomization or lactating.
* Have a concurrent malignancy or had another malignancy within 5 years (=5 years) of study enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/07/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/07/2022
Sample size
Target
Accrual to date
Final
530
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Adelaide
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Footscray
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Randwick
Recruitment hospital [4] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Subiaco
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3011 - Footscray
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Hawaii
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oklahoma
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Belgium
State/province [23] 0 0
Wilrijk
Country [24] 0 0
Canada
State/province [24] 0 0
Toronto
Country [25] 0 0
Canada
State/province [25] 0 0
Vancouver
Country [26] 0 0
Denmark
State/province [26] 0 0
Herlev
Country [27] 0 0
Denmark
State/province [27] 0 0
Odense
Country [28] 0 0
France
State/province [28] 0 0
Caen
Country [29] 0 0
France
State/province [29] 0 0
Lille
Country [30] 0 0
France
State/province [30] 0 0
Lyon
Country [31] 0 0
France
State/province [31] 0 0
Montpellier
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Rennes
Country [34] 0 0
Germany
State/province [34] 0 0
Dusseldorf
Country [35] 0 0
Germany
State/province [35] 0 0
Freiburg
Country [36] 0 0
Germany
State/province [36] 0 0
Homburg
Country [37] 0 0
Germany
State/province [37] 0 0
Jena
Country [38] 0 0
Germany
State/province [38] 0 0
Marburg
Country [39] 0 0
Germany
State/province [39] 0 0
Tubingen
Country [40] 0 0
Greece
State/province [40] 0 0
Athens
Country [41] 0 0
Greece
State/province [41] 0 0
Heraklion
Country [42] 0 0
Greece
State/province [42] 0 0
Patras
Country [43] 0 0
Greece
State/province [43] 0 0
Thessaloniki
Country [44] 0 0
Hungary
State/province [44] 0 0
Budapest
Country [45] 0 0
Hungary
State/province [45] 0 0
Miskolc
Country [46] 0 0
Israel
State/province [46] 0 0
Haifa
Country [47] 0 0
Israel
State/province [47] 0 0
Kfar Saba
Country [48] 0 0
Israel
State/province [48] 0 0
Petach Tikva
Country [49] 0 0
Israel
State/province [49] 0 0
Tel Hashomer
Country [50] 0 0
Israel
State/province [50] 0 0
Tel-Aviv
Country [51] 0 0
Israel
State/province [51] 0 0
Zerifin
Country [52] 0 0
Italy
State/province [52] 0 0
Arezzo
Country [53] 0 0
Italy
State/province [53] 0 0
Bologna
Country [54] 0 0
Italy
State/province [54] 0 0
Milano
Country [55] 0 0
Italy
State/province [55] 0 0
Orbassano
Country [56] 0 0
Italy
State/province [56] 0 0
Rome
Country [57] 0 0
Italy
State/province [57] 0 0
Verona
Country [58] 0 0
Japan
State/province [58] 0 0
Bunkyo-ku
Country [59] 0 0
Japan
State/province [59] 0 0
Chiba
Country [60] 0 0
Japan
State/province [60] 0 0
Fukuoka
Country [61] 0 0
Japan
State/province [61] 0 0
Hidaka
Country [62] 0 0
Japan
State/province [62] 0 0
Hirosaki
Country [63] 0 0
Japan
State/province [63] 0 0
Kashiwa
Country [64] 0 0
Japan
State/province [64] 0 0
Kita-gun
Country [65] 0 0
Japan
State/province [65] 0 0
Kobe
Country [66] 0 0
Japan
State/province [66] 0 0
Matsuyama
Country [67] 0 0
Japan
State/province [67] 0 0
Morioka
Country [68] 0 0
Japan
State/province [68] 0 0
Niigata
Country [69] 0 0
Japan
State/province [69] 0 0
Osaka
Country [70] 0 0
Japan
State/province [70] 0 0
Sapporo
Country [71] 0 0
Japan
State/province [71] 0 0
Sendai
Country [72] 0 0
Japan
State/province [72] 0 0
Suita-shi
Country [73] 0 0
Japan
State/province [73] 0 0
Tokyo
Country [74] 0 0
Japan
State/province [74] 0 0
Tsukuba
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Daejeon
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Seongnam-si
Country [77] 0 0
Korea, Republic of
State/province [77] 0 0
Seongnam
Country [78] 0 0
Korea, Republic of
State/province [78] 0 0
Seoul
Country [79] 0 0
Mexico
State/province [79] 0 0
Aguascalientes
Country [80] 0 0
Mexico
State/province [80] 0 0
Culiacan
Country [81] 0 0
Mexico
State/province [81] 0 0
Mexico
Country [82] 0 0
Mexico
State/province [82] 0 0
Monterrey
Country [83] 0 0
Mexico
State/province [83] 0 0
Morelia
Country [84] 0 0
Netherlands
State/province [84] 0 0
Amsterdam
Country [85] 0 0
Netherlands
State/province [85] 0 0
Arnhem
Country [86] 0 0
Netherlands
State/province [86] 0 0
Maastricht
Country [87] 0 0
Netherlands
State/province [87] 0 0
Rotterdam
Country [88] 0 0
Netherlands
State/province [88] 0 0
Sittard
Country [89] 0 0
Poland
State/province [89] 0 0
Gdansk
Country [90] 0 0
Poland
State/province [90] 0 0
Poznan
Country [91] 0 0
Poland
State/province [91] 0 0
Warszawa
Country [92] 0 0
Poland
State/province [92] 0 0
Wieliszew
Country [93] 0 0
Romania
State/province [93] 0 0
Baia Mare
Country [94] 0 0
Romania
State/province [94] 0 0
Cluj-Napoca
Country [95] 0 0
Romania
State/province [95] 0 0
Craiova
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Ivanovo
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Kazan
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Moscow
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Saint Petersburg
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Saratov
Country [101] 0 0
Spain
State/province [101] 0 0
Badajoz
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
Country [103] 0 0
Spain
State/province [103] 0 0
Madrid
Country [104] 0 0
Taiwan
State/province [104] 0 0
Kaohsiung
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taichung
Country [106] 0 0
Taiwan
State/province [106] 0 0
Tainan
Country [107] 0 0
Taiwan
State/province [107] 0 0
Taipei
Country [108] 0 0
Turkey
State/province [108] 0 0
Ankara
Country [109] 0 0
Turkey
State/province [109] 0 0
Antalya
Country [110] 0 0
Turkey
State/province [110] 0 0
Edirne
Country [111] 0 0
Turkey
State/province [111] 0 0
Istanbul
Country [112] 0 0
Turkey
State/province [112] 0 0
Malatya
Country [113] 0 0
Ukraine
State/province [113] 0 0
Dnipropetrovsk
Country [114] 0 0
Ukraine
State/province [114] 0 0
Kyiv
Country [115] 0 0
Ukraine
State/province [115] 0 0
Lutsk
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Bebington
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Chelsea
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Nottingham
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Southampton
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02426125
Trial related presentations / publications
van der Heijden MS, Powles T, Petrylak D, de Wit R, Necchi A, Sternberg CN, Matsubara N, Nishiyama H, Castellano D, Hussain SA, Bamias A, Gakis G, Lee JL, Tagawa ST, Vaishampayan U, Aragon-Ching JB, Eigl BJ, Hozak RR, Rasmussen ER, Xia MS, Rhodes R, Wijayawardana S, Bell-McGuinn KM, Aggarwal A, Drakaki A. Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial. Nat Commun. 2022 Apr 6;13(1):1878. doi: 10.1038/s41467-022-29441-y.
Mitani S, Chen Y, Inoue K, Mori J, Gao L, Long A, Wakabayashi S. Clinical Impact of a Shortened Infusion Duration of Ramucirumab in Japanese Patients -A Model-Based Approach. Gan To Kagaku Ryoho. 2021 Nov;48(11):1381-1387.
Necchi A, Nishiyama H, Matsubara N, Lee JL, Petrylak DP, de Wit R, Drakaki A, Liepa AM, Mao H, Bell-McGuinn K, Powles T. Health-related quality of life in the randomized phase 3 study of ramucirumab plus docetaxel versus placebo plus docetaxel in platinum-refractory advanced urothelial carcinoma (RANGE). BMC Urol. 2020 Nov 7;20(1):181. doi: 10.1186/s12894-020-00752-w.
Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, Castellano D, Hussain SA, Flechon A, Bamias A, Yu EY, van der Heijden MS, Matsubara N, Alekseev B, Necchi A, Geczi L, Ou YC, Coskun HS, Su WP, Bedke J, Gakis G, Percent IJ, Lee JL, Tucci M, Semenov A, Laestadius F, Peer A, Tortora G, Safina S, Garcia Del Muro X, Rodriguez-Vida A, Cicin I, Harputluoglu H, Tagawa ST, Vaishampayan U, Aragon-Ching JB, Hamid O, Liepa AM, Wijayawardana S, Russo F, Walgren RA, Zimmermann AH, Hozak RR, Bell-McGuinn KM, Powles T; RANGE study investigators. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):105-120. doi: 10.1016/S1470-2045(19)30668-0. Epub 2019 Nov 18.
Petrylak DP, de Wit R, Chi KN, Drakaki A, Sternberg CN, Nishiyama H, Castellano D, Hussain S, Flechon A, Bamias A, Yu EY, van der Heijden MS, Matsubara N, Alekseev B, Necchi A, Geczi L, Ou YC, Coskun HS, Su WP, Hegemann M, Percent IJ, Lee JL, Tucci M, Semenov A, Laestadius F, Peer A, Tortora G, Safina S, Del Muro XG, Rodriguez-Vida A, Cicin I, Harputluoglu H, Widau RC, Liepa AM, Walgren RA, Hamid O, Zimmermann AH, Bell-McGuinn KM, Powles T; RANGE study investigators. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial. Lancet. 2017 Nov 18;390(10109):2266-2277. doi: 10.1016/S0140-6736(17)32365-6. Epub 2017 Sep 12.
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02426125