Phase 3
Completed N=1,560
Study Comparing Orteronel Plus Prednisone in Participants With Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
Source: ClinicalTrials.gov NCT01193244 ↗Enrolled (actual)
1,560
Serious AEs
45.1%
Results posted
May 2017
Primary outcomePrimary: Radiographic Progression-free Survival (rPFS) — 8.7; 13.8 months — p=<0.00001
◆ Published Evidence
Highly cited
231citations · ~29 / year
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.
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)
Linked Publications (3)
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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.
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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.
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Physiologically based and population PK modeling in optimizing drug development: A predict-learn-confirm analysis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Radiographic Progression-free Survival (rPFS) |
8.7; 13.8 | <0.00001 sig |
| PRIMARY Overall Survival |
29.5; 29.9 | 0.59755 |
| SECONDARY Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50) Response at Week 12 |
24.6; 42.6 | <0.001 sig |
| SECONDARY Percentage of Participants With Favorable Circulating Tumor Cell Count (CTC) Levels at Week 12 |
9.1; 15.4 | 0.001 sig |
| SECONDARY Time to Pain Progression |
NA; NA | 0.33906 |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
733; 769; 321; 380 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events Greater Than or Equal to (>=) Grade 3 |
405; 537; 78; 77 | — |
| SECONDARY Number of Participants With TEAEs Related to Vital Signs |
76; 98; 26; 41; 12; 26 | — |
| SECONDARY Number of Participants With TEAEs Related to Weight |
47; 119; 36; 10 | — |
| SECONDARY Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status |
251; 200; 177; 237; 47; 66 | — |
| SECONDARY Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings |
130; 163 | — |
| SECONDARY Worst Change From Baseline Over Time in Cardiac Ejection Fraction |
-3.8; -4.8 | — |
| SECONDARY Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Coagulation |
215; 399; 114; 107; 204; 336 | — |
| SECONDARY Percentage of Participants With Skeletal Related Events (SRE) |
10.9; 8.6 | — |
| SECONDARY Time to SRE |
9.0; 13.9 | — |
| SECONDARY Percentage of Participants Achieving PSA50 Response at Any Time During the Study |
28.09; 49.70; 34.94; 54.81; 36.99; 56.00 | — |
| SECONDARY Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12 |
5.4; 16.7 | — |
| SECONDARY Percentage of Participants Achieving PSA90 Response at Any Time During the Study |
5.39; 16.67; 8.69; 22.22; 11.64; 26.44 | — |
| SECONDARY Time to PSA Progression |
5.59; 8.3 | — |
| SECONDARY Time to Docetaxel Chemotherapy |
19.0; 23.0 | — |
| SECONDARY Time to Subsequent Antineoplastic Therapy |
13.9; 17.2 | — |
| SECONDARY Percentage of Participants With Objective Response |
15.2; 34.7 | — |
| SECONDARY Time to Deterioration in Global Health Status |
10.7; 8.3 | — |
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
Data sourced from ClinicalTrials.gov (NCT01193244) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.