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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01193257




Registration number
NCT01193257
Ethics application status
Date submitted
31/08/2010
Date registered
1/09/2010
Date last updated
19/12/2018

Titles & IDs
Public title
Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer.
Scientific title
A Phase 3, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or Following Docetaxel-based Therapy.
Secondary ID [1] 0 0
2010-018662-23
Secondary ID [2] 0 0
C21005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

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

Experimental: Orteronel + prednisone -

Placebo comparator: Placebo + prednisone -


Treatment: Drugs: Orteronel
Orteronel tablets

Treatment: Drugs: Prednisone
Prednisone tablets

Treatment: Drugs: Orteronel Placebo
Orteronel placebo-matching tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
Baseline until death (approximately up to 4.5 years)
Secondary outcome [1] 0 0
Radiographic Progression-free Survival (rPFS)
Timepoint [1] 0 0
Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
Secondary outcome [2] 0 0
Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50 Response) at Week 12
Timepoint [2] 0 0
Week 12
Secondary outcome [3] 0 0
Percentage of Participants With Pain Response at Week 12
Timepoint [3] 0 0
Week 12
Secondary outcome [4] 0 0
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Timepoint [4] 0 0
Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
Secondary outcome [5] 0 0
Number of Participants With Abnormal Physical Examination Findings
Timepoint [5] 0 0
Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
Secondary outcome [6] 0 0
Number of Participants With TEAEs Related to Vital Signs
Timepoint [6] 0 0
Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
Secondary outcome [7] 0 0
Number of Participants With TEAEs Related to Weight
Timepoint [7] 0 0
Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
Secondary outcome [8] 0 0
Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
Timepoint [8] 0 0
Baseline up to End-of-treatment (EOT) (Cycle 59 Day 58)
Secondary outcome [9] 0 0
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings
Timepoint [9] 0 0
Cycle 59 Day 58
Secondary outcome [10] 0 0
Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel
Timepoint [10] 0 0
Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
Secondary outcome [11] 0 0
Percentage of Participants Achieving PSA50 Response at Any Time During the Study
Timepoint [11] 0 0
Cycle: 4, 7, 10, 13, 16, 19, 22, and 25
Secondary outcome [12] 0 0
Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12
Timepoint [12] 0 0
Week 12
Secondary outcome [13] 0 0
Percentage of Participants Achieving PSA90 Response at Any Time During the Study
Timepoint [13] 0 0
Cycle: 7, 10, 13, 16, 19, 22, and 25
Secondary outcome [14] 0 0
Best PSA Response at Any Time During the Study
Timepoint [14] 0 0
Cycle: 4, 7, 10, 13, 16, 19, 22, and 25
Secondary outcome [15] 0 0
Time to PSA Progression
Timepoint [15] 0 0
Baseline until the final on treatment assessment or until end of short term follow-up following discontinuation of treatment, whichever occurred later (approximately up to 4.5 years)
Secondary outcome [16] 0 0
Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC)
Timepoint [16] 0 0
Baseline and EOT (Cycle 59 Day 58)
Secondary outcome [17] 0 0
Percentage of Participants With Objective Response
Timepoint [17] 0 0
Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
Secondary outcome [18] 0 0
Time to Pain Progression
Timepoint [18] 0 0
Baseline until EOT visit or until end of short term follow-up, whichever occurred later (approximately up to 4.5 years)
Secondary outcome [19] 0 0
Time to Pain Response
Timepoint [19] 0 0
Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
Secondary outcome [20] 0 0
Number of Participants With Best Pain Response
Timepoint [20] 0 0
Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
Secondary outcome [21] 0 0
Percentage of Participants With Health-related Quality of Life (HRQOL) Response at Week 12
Timepoint [21] 0 0
Week 12

Eligibility
Key inclusion criteria
Each participant must meet all of the following inclusion criteria:

* Voluntary written consent
* Male 18 years or older
* Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma
* Radiograph-documented metastatic disease
* Progressive disease
* Prior surgical castration or concurrent use of an agent for medical castration
* Progressive disease during or following 1 or 2 regimens of cytotoxic chemotherapy, 1 of which must have included docetaxel. Must have received greater than or equal to (>=) 360 milligram per square meter (mg/m^2) of docetaxel within a 6-month period. Participants who were clearly intolerant to docetaxel or develop progressive disease before receiving >= 360 mg/m^2 are also eligible if they have received at least 225 mg/m^2 of docetaxel within a 6-month period and meet the other study entry criteria.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
* Even if surgically sterilized, participants must practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, OR Abstain from heterosexual intercourse
* Screening laboratory values as specified in protocol
* Stable medical condition
* Life expectancy of 6 months or more
* Participants who have had up to 2 prior chemotherapy treatments are eligible to participate
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

* Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue
* Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone
* Any other therapies for prostate cancer, except for GnRH analogue therapy, must be discontinued 2 weeks before the first dose of study drug
* Radioisotope therapy or external beam radiation therapy within 4 weeks of first dose of study drug
* Documented central nervous system metastases
* Treatment with any investigational compound within 30 days prior to first dose of study drug (Participants who are in long-term follow-up following active treatment in other trials are eligible)
* Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
* Uncontrolled cardiovascular condition as specified in study protocol
* Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
* Unwilling or unable to comply with protocol
* Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
* Uncontrolled nausea, vomiting, or diarrhea despite appropriate medical therapy
* Prostate cancer confined to just the prostrate bed or immediate adjacent tissue

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
15/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/02/2016
Sample size
Target
Accrual to date
Final
1099
Recruitment in Australia
Recruitment state(s)
QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
- Redcliffe
Recruitment hospital [2] 0 0
- Woodville South
Recruitment hospital [3] 0 0
- Hobart
Recruitment hospital [4] 0 0
- Malvere
Recruitment hospital [5] 0 0
- Wodonga
Recruitment postcode(s) [1] 0 0
- Redcliffe
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
- Hobart
Recruitment postcode(s) [4] 0 0
- Malvere
Recruitment postcode(s) [5] 0 0
- Wodonga
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
United States of America
State/province [22] 0 0
Washington
Country [23] 0 0
Belgium
State/province [23] 0 0
Brussels
Country [24] 0 0
Belgium
State/province [24] 0 0
Kortijk
Country [25] 0 0
Belgium
State/province [25] 0 0
Liege
Country [26] 0 0
Belgium
State/province [26] 0 0
Namur
Country [27] 0 0
Canada
State/province [27] 0 0
Alberta
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
New Brunswick
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Czechia
State/province [32] 0 0
Hradec Dralove
Country [33] 0 0
Czechia
State/province [33] 0 0
Kromertz
Country [34] 0 0
Czechia
State/province [34] 0 0
Modrice
Country [35] 0 0
Czechia
State/province [35] 0 0
Praha
Country [36] 0 0
Czechia
State/province [36] 0 0
Zlin
Country [37] 0 0
Estonia
State/province [37] 0 0
Tallinn
Country [38] 0 0
Finland
State/province [38] 0 0
Oulu
Country [39] 0 0
Finland
State/province [39] 0 0
Tampere
Country [40] 0 0
France
State/province [40] 0 0
La Roche-sur-Yon
Country [41] 0 0
France
State/province [41] 0 0
Le Mans
Country [42] 0 0
France
State/province [42] 0 0
Lyon Cedex
Country [43] 0 0
France
State/province [43] 0 0
Lyon
Country [44] 0 0
France
State/province [44] 0 0
Marseille
Country [45] 0 0
France
State/province [45] 0 0
Paris
Country [46] 0 0
France
State/province [46] 0 0
Villejuif cedex
Country [47] 0 0
Greece
State/province [47] 0 0
Patras
Country [48] 0 0
Hungary
State/province [48] 0 0
Miskolc
Country [49] 0 0
Hungary
State/province [49] 0 0
Osztaly
Country [50] 0 0
Italy
State/province [50] 0 0
Novara
Country [51] 0 0
Italy
State/province [51] 0 0
Rome
Country [52] 0 0
Netherlands
State/province [52] 0 0
Eindhoven
Country [53] 0 0
Poland
State/province [53] 0 0
Bielsko-Biala
Country [54] 0 0
Poland
State/province [54] 0 0
Goczalkowice-Zdroj
Country [55] 0 0
Poland
State/province [55] 0 0
Wroclaw
Country [56] 0 0
Spain
State/province [56] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double-blind, multicenter, phase 3 study evaluating orteronel plus prednisone compared with placebo plus prednisone in men with metastatic, castration-resistant prostate cancer (mCRPC) that has progressed following Docetaxel-based therapy
Trial website
https://clinicaltrials.gov/study/NCT01193257
Trial related presentations / publications
Heller G, McCormack R, Kheoh T, Molina A, Smith MR, Dreicer R, Saad F, de Wit R, Aftab DT, Hirmand M, Limon A, Fizazi K, Fleisher M, de Bono JS, Scher HI. Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials. J Clin Oncol. 2018 Feb 20;36(6):572-580. doi: 10.1200/JCO.2017.75.2998. Epub 2017 Dec 22.
Suri A, Chapel S, Lu C, Venkatakrishnan K. Physiologically based and population PK modeling in optimizing drug development: A predict-learn-confirm analysis. Clin Pharmacol Ther. 2015 Sep;98(3):336-44. doi: 10.1002/cpt.155. Epub 2015 Jul 14.
Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol. 2015 Mar 1;33(7):723-31. doi: 10.1200/JCO.2014.56.5119. Epub 2015 Jan 26.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Millennium Pharmaceuticals, Inc.
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/NCT01193257