Clinical trial NCT01193244: Study Comparing Orteronel Plus Prednisone in Participants With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 3, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel Plus Prednisone With Placebo Plus Prednisone in Patients With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-09-01
Enrollment: 1560
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 (TAK-700) plus prednisone compared with placebo plus prednisone in the treatment of men with progressive, chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC)


Eligibility criteria: Inclusion Criteria:

Each patient must meet all of the following inclusion criteria:

* Voluntary written consent
* Male patients 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
* Either absence of pain or pain not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to study entry
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
* Even if surgically sterilized, patients must practice effective barrier contraception during the entire study treatment and for 4 months after the last dose of study drug, OR abstain from heterosexual intercourse
* Meet screening laboratory values as specified in protocol
* Stable medical condition

Exclusion Criteria:

Patients 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
* Received antiandrogen therapy within 6 weeks for bicalutamide and 4 weeks for all others prior to first dose of study drug
* Continuous daily use of oral prednisone or oral dexamethasone for more than 14 days within 3 months prior to study
* Received prior chemotherapy for prostate cancer with exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening
* Exposure to radioisotope therapy within 4 weeks of receiving first dose of study drug; exposure to external beam radiation within 2 weeks of start of screening until receiving the 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
* Current spinal cord compression, bilateral hydronephrosis or current bladder neck outlet obstruction
* 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
* Uncontrolled nausea, vomiting or diarrhea
* Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel

Primary outcomes:
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: Baseline until radiographic disease progression or death, whichever occurred first (approximately up to 4.7 years)
measure: Overall Survival
timeFrame: Baseline until death (up to 4.7 years)
Secondary outcomes:
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 Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12
timeFrame: Week 12
measure: Time to Pain Progression
timeFrame: Baseline until End of treatment (EOT) (approximately up to 4.7 years)
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)
measure: Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 61 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 61 Day 58)
measure: Number of Participants With TEAEs Related to Weight
timeFrame: Baseline up to 30 days after last dose of study drug (Cycle 61 Day 58)
measure: Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status
timeFrame: Baseline until EOT (approximately up to 4.7 years)
measure: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Baseline up to EOT (Cycle 61 Day 58)
measure: Worst Change From Baseline Over Time in Cardiac Ejection Fraction
timeFrame: Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)
measure: Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation
timeFrame: Baseline up to 30 days or EOT whichever is later (approximately up to Cycle 61 Day 58)
measure: Percentage of Participants With Skeletal Related Events (SRE)
timeFrame: Baseline up to EOT (approximately up to 4.7 years)
measure: Time to SRE
timeFrame: Baseline up to EOT (Cycle 61 Day 58)
measure: Percentage of Participants Achieving PSA50 Response at Any Time During the Study
timeFrame: Cycle: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37
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: 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34 and 37
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 4.7 years)
measure: Time to Docetaxel Chemotherapy
timeFrame: Baseline until start of docetaxel chemotherapy (up to 4.7 years)
measure: Time to Subsequent Antineoplastic Therapy
timeFrame: Baseline until start of subsequent antineoplastic therapy (up to 4.7 years)
measure: Percentage of Participants With Objective Response
timeFrame: Baseline until disease progression or death, whichever occurred first (approximately up to 4.7 years)
measure: Time to Deterioration in Global Health Status
timeFrame: Baseline until EOT (approximately up to 4.7 years)
Other outcomes:
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state: Florida
city: Fort Myers
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city: Orlando
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city: Port St Lucie
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state: Indiana
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city: New Orleans
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state: Louisiana
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state: Massachusetts
city: Lansing
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state: Minnesota
city: Corinth
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state: Mississippi
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state: Missouri
city: Jefferson City
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state: Missouri
city: Omaha
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state: Nebraska
city: Las Vegas
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state: Nevada
city: Hackensack
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state: New Jersey
city: East Syracuse
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state: New York
city: New York
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city: Durham
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state: North Carolina
city: Raleigh
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state: North Carolina
city: Kettering
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state: Oregon
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state: Pennsylvania
city: Lancaster
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city: Santiago
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city: Praha 4
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city: Joensuu
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city: Oulu
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city: Angers
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city: Bordeaux
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city: Caen
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city: La Roche Sur Yon
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city: Lyon
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city: Paris Cedex 13
country: France
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city: Poitiers
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city: Braunschweig
country: Germany
city: Dresden
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city: Hamburg
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city: Athens
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city: Heraklion Crete
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country: Japan
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country: Japan
city: Sendai City
country: Japan
city: Shimizucho Sunto-gun
country: Japan
city: Suntou-gun
country: Japan
city: Tokyo
country: Japan
city: Yamagata City
country: Japan
city: Yokohama City
country: Japan
city: Yufu-city
country: Japan
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Klaipeda
country: Lithuania
city: Vilnius
country: Lithuania
city: Durango Durango
country: Mexico
city: Mexico City Distrito Federal
country: Mexico
city: Zapopan Jalisco
country: Mexico
city: Amsterdam
country: Netherlands
city: Arnhem
country: Netherlands
city: Breda
country: Netherlands
city: Eindhoven
country: Netherlands
city: Heerlen
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Dunedin
country: New Zealand
city: Takapuna
country: New Zealand
city: Tauranga
country: New Zealand
city: Lima
country: Peru
city: Bielsko-biala
country: Poland
city: Wroclaw
country: Poland
city: Liepaja
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: San Juan
country: Puerto Rico
city: Bucharest
country: Romania
city: Cluj-napoca
country: Romania
city: Moscow
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Nitra
country: Slovakia
city: Presov
country: Slovakia
city: Trencin
country: Slovakia
city: Zilina
country: Slovakia
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: George
country: South Africa
city: Port Elizabeth
country: South Africa
city: Barcelona
country: Spain
city: La Coruna
country: Spain
city: Madrid
country: Spain
city: Majadahonda
country: Spain
city: Pamplona
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Goteborg
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Aarau
country: Switzerland
city: Lausanne
country: Switzerland
city: Winterthur
country: Switzerland
city: Zurich
country: Switzerland
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kyiv
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Aberdeen
country: United Kingdom
city: Belfast
country: United Kingdom
city: Bristol
country: United Kingdom
city: Cottingham
country: United Kingdom
city: Coventry
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Northwood
country: United Kingdom
city: Preston
country: United Kingdom
city: Southampton
country: United Kingdom
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: Saad F, Fizazi K, Jinga V, Efstathiou E, Fong PC, Hart LL, Jones R, McDermott R, Wirth M, Suzuki K, MacLean DB, Wang L, Akaza H, Nelson J, Scher HI, Dreicer R, Webb IJ, de Wit R; ELM-PC 4 investigators. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015 Mar;16(3):338-48. doi: 10.1016/S1470-2045(15)70027-6. Epub 2015 Feb 18.