Clinical trial NCT01193257: Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer.
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-09-01
Enrollment: 1099
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

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

Primary outcomes:
measure: Overall Survival
timeFrame: Baseline until death (approximately up to 4.5 years)
Secondary outcomes:
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
measure: Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50 Response) at Week 12
timeFrame: Week 12
measure: Percentage of Participants With Pain Response at Week 12
timeFrame: Week 12
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
measure: Number of Participants With Abnormal Physical Examination Findings
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
measure: Number of Participants With TEAEs Related to Weight
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
measure: Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
timeFrame: Baseline up to End-of-treatment (EOT) (Cycle 59 Day 58)
measure: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Cycle 59 Day 58
measure: Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 59 Day 58)
measure: Percentage of Participants Achieving PSA50 Response at Any Time During the Study
timeFrame: Cycle: 4, 7, 10, 13, 16, 19, 22, and 25
measure: Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving PSA90 Response at Any Time During the Study
timeFrame: Cycle: 7, 10, 13, 16, 19, 22, and 25
measure: Best PSA Response at Any Time During the Study
timeFrame: Cycle: 4, 7, 10, 13, 16, 19, 22, and 25
measure: Time to PSA Progression
timeFrame: 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)
measure: Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC)
timeFrame: Baseline and EOT (Cycle 59 Day 58)
measure: Percentage of Participants With Objective Response
timeFrame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
measure: Time to Pain Progression
timeFrame: Baseline until EOT visit or until end of short term follow-up, whichever occurred later (approximately up to 4.5 years)
measure: Time to Pain Response
timeFrame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
measure: Number of Participants With Best Pain Response
timeFrame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.5 years)
measure: Percentage of Participants With Health-related Quality of Life (HRQOL) Response at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Anchorage
country: United States
state: Alaska
city: Fort Smith
country: United States
state: Arkansas
city: Fountain Valley
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Riverside
country: United States
state: California
city: San Diego
country: United States
state: California
city: Fort Myers
country: United States
state: Florida
city: Port Saint Lucie
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Jeffersonville
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Westminster
country: United States
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Jefferson City
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Hackensack
country: United States
state: New Jersey
city: Albany
country: United States
state: New York
city: East Syracuse
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Tualatin
country: United States
state: Oregon
city: Lancaster
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Greenville
country: United States
state: South Carolina
city: Chattanooga
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Webster
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Newport News
country: United States
state: Virginia
city: Kennewick
country: United States
state: Washington
city: Redcliffe
country: Australia
state: Queensland
city: Woodville South
country: Australia
state: South Australia
city: Hobart
country: Australia
state: Tasmania
city: Malvere
country: Australia
state: Victoria
city: Wodonga
country: Australia
state: Victoria
city: Brussels
country: Belgium
city: Kortijk
country: Belgium
city: Liege
country: Belgium
city: Namur
country: Belgium
city: Edmonton
country: Canada
state: Alberta
city: Kelowna
country: Canada
state: British Columbia
city: Moncton
country: Canada
state: New Brunswick
city: Brampton
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Greenfield Park
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Pointe-Claire
country: Canada
state: Quebec
city: Hradec Dralove
country: Czechia
city: Kromertz
country: Czechia
city: Modrice
country: Czechia
city: Praha
country: Czechia
city: Zlin
country: Czechia
city: Tallinn
country: Estonia
city: Oulu
country: Finland
city: Tampere
country: Finland
city: La Roche-sur-Yon
country: France
city: Le Mans
country: France
city: Lyon Cedex
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Paris
country: France
city: Villejuif cedex
country: France
city: Patras
country: Greece
city: Miskolc
country: Hungary
city: Osztaly
country: Hungary
city: Novara
country: Italy
city: Rome
country: Italy
city: Eindhoven
country: Netherlands
city: Bielsko-Biala
country: Poland
city: Goczalkowice-Zdroj
country: Poland
city: Wroclaw
country: Poland
city: Sevilla
country: Spain
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.