Phase 3
Completed N=1,099
Study Comparing Orteronel Plus Prednisone in Participants With Metastatic Castration-Resistant Prostate Cancer.
Source: ClinicalTrials.gov NCT01193257 ↗Enrolled (actual)
1,099
Serious AEs
48.6%
Results posted
Dec 2018
Primary outcomePrimary: Overall Survival — 15.3; 17.1 months — p=0.12085
◆ Published Evidence
Highly cited
230citations · ~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 plus prednisone compared with placebo plus prednisone in men with metastatic, castration-resistant prostate cancer (mCRPC) that has progressed following Docetaxel-based therapy
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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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.
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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 Overall Survival |
15.3; 17.1 | 0.12085 |
| SECONDARY Radiographic Progression-free Survival (rPFS) |
5.7; 8.3 | 0.00038 sig |
| SECONDARY Percentage of Participants Achieving 50 Percent Reduction From Baseline in Prostate Specific Antigen (PSA50 Response) at Week 12 |
9.9; 24.9 | < 0.0001 sig |
| SECONDARY Percentage of Participants With Pain Response at Week 12 |
9.0; 12.1 | 0.12778 |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) |
345; 719 | — |
| SECONDARY Number of Participants With Abnormal Physical Examination Findings |
0; 1 | — |
| SECONDARY Number of Participants With TEAEs Related to Vital Signs |
21; 83; 8; 31; 18; 51 | — |
| SECONDARY Number of Participants With TEAEs Related to Weight |
32; 107; 7; 6 | — |
| SECONDARY Number of Participants With Worst Change From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status |
56; 112; 70; 121; 13; 47 | — |
| SECONDARY Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings |
1; 3 | — |
| SECONDARY Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Steroid Hormone Panel |
9; 140; 13; 41; 14; 38 | — |
| SECONDARY Percentage of Participants Achieving PSA50 Response at Any Time During the Study |
12.72; 32.74; 18.40; 38.21; 22.55; 36.70 | — |
| SECONDARY Percentage of Participants Achieving 90 Percent Reduction From Baseline in Prostate Specific Antigen (PSA90 Response) at Week 12 |
2.83; 9.66 | — |
| SECONDARY Percentage of Participants Achieving PSA90 Response at Any Time During the Study |
4.91; 14.89; 6.86; 14.23; 7.27; 15.20 | — |
| SECONDARY Best PSA Response at Any Time During the Study |
— | — |
| SECONDARY Time to PSA Progression |
2.9; 5.5 | — |
| SECONDARY Number of Participants With Shifts From Baseline Between Favorable and Unfavorable Categories in Circulating Tumor Cell Count (CTC) |
27; 63; 30; 40; 8; 23 | — |
| SECONDARY Percentage of Participants With Objective Response |
2.7; 17.1 | — |
| SECONDARY Time to Pain Progression |
22.0; 24.2 | — |
| SECONDARY Time to Pain Response |
NA; NA | — |
| SECONDARY Number of Participants With Best Pain Response |
72; 166 | — |
| SECONDARY Percentage of Participants With Health-related Quality of Life (HRQOL) Response at Week 12 |
9.9; 8.7 | — |
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
Data sourced from ClinicalTrials.gov (NCT01193257) 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.