Primary Objective:• To determine if orteronel plus prednisone improves overall survival (OS)Key Secondary Objectives: • To determine if orteronel plus prednisone improves radiographic progression-free survival (rPFS)• To determine if orteronel plus…
ID
Source
Brief title
Condition
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall survival
Secondary outcome
rPFS
50% PSA response at 12 weeks
Pain response rate at 12 weeks
Background summary
Orteronel (TAK-700) is an orally bioavailable, reversible, nonsteroidal
inhibitor of 17,20-lyase, a key enzyme in androgen synthesis. This study is
designed to investigate whether the androgen synthesis inhibitor orteronel
improves overall survival (OS) in men with progressive, metastatic,
castration-resistant prostate cancer (mCRPC) that has progressed following at
least 1 or 2 prior cytotoxic chemotherapies, 1 of which must have included
docetaxel.
Study objective
Primary Objective:
• To determine if orteronel plus prednisone improves overall survival (OS)
Key Secondary Objectives:
• To determine if orteronel plus prednisone improves radiographic
progression-free survival (rPFS)
• To determine if orteronel plus prednisone improves 50% prostate-specific
antigen (PSA) response rate at 12 weeks
• To evaluate if orteronel plus prednisone improves pain response at 12 weeks
Exploratory Objectives:
• To assess tumor specimens for candidate biomarkers predictive of orteronel
antitumor activity including, but not limited to, the TMPRSS2:ERG fusion gene
• To evaluate polymorphisms in the CYP17 gene and other germline genes
implicated in the safety or efficacy of orteronel
• To assess the functioning and symptom QOL subscales of the European
Organization for Research and Treatment of Cancer Quality of Life Questionnaire
Core Module 30 (EORTC QLQ-C30)
• To evaluate medical resource utilization (MRU) and calculate utility values
using a preference-based patient-reported outcome (PRO) instrument (European
Quality of Life 5-Dimensional [EQ-5D]), while patients are on study treatment
Study design
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). Gonadotropin
releasing hormone (GnRH) analogue therapy will be continued unless the patient
is surgically castrate. Patients must have evidence of disease progression
during or after a minimum of 6 standard cycles (75 mg/m2/cycle) of docetaxel,
or a total of >= 450 mg/m2. Patients who were clearly intolerant to docetaxel
before receiving >= 450 mg/m2 are also eligible if they have received at least 3
standard cycles or >= 225 mg/m2 as local standard of care and meet the other
study entry criteria. One formal interim analysis is planned for this study.
Patients will return for regularly scheduled study visits (treatment/short-term
follow-up) for as long as they: 1) continue to take study drug, or 2)
discontinue study drug but have not yet experienced disease progression.
Patients will discontinue scheduled study visits if they experience disease
progression and decide to discontinue study drug. Patients may remain on study
drug after disease progression and return for scheduled visits (short-term
follow-up) until they receive subsequent antineoplastic therapy.
All patients will be followed for survival (long-term follow-up) after
discontinuing the treatment/short-term follow-up portion of the study.
Long-term follow-up will continue until death or discontinuation of the study
by the sponsor.
Intervention
Twice a day 400 mg orteronel or placebo (oral)
Twice a day 5 mg prednison (oral)
Study burden and risks
Extra procedures: MUGA/ECHO (Screening, Cyclus (C) 4, C7, C13, Q6C, EOT); ECG
(Scr, C2, C7, C13, EOT); CT/MRI and botscan (Scr, C3, C5, C7, C10, C13, Q3C).
The subjects have to take studymedication plus prednison twice a day on
determined times.
The subjects have to register in their diaries the time they take the
studymedication and prednison. It is expected that they complete the diaries
and bring it with them during each visit.
The subjects have to complete 3 different questionnaires regarding pain,
quality of life and health status.
Patients who received orteronel, experienced the following adverse events:
fatigue, headache, elevated aminotransferases, a decrease in LVEF, itching and
rash, decreased preformance, worsened but controlled hypertension, episodic
nausea, vomiting, diarrhea and dehydration (see IB for detailed information on
safety).
40 Landsdown Street
Cambridge, MA USA 02139
US
40 Landsdown Street
Cambridge, MA USA 02139
US
Listed location countries
Age
Inclusion criteria
1. Male patients 18 years or older.
2. Voluntary written consent
3. Adenocarcinoma of the prostate histologically or cytologically confirmed.
4. Metastatic disease radiographically documented (CT/MRI, bone scan).
5. Progressive disease
6. Prior surgical castration or concurrent use of an agent for medical castration
7. Screening PSA >= 2 ng/ml.
8. Must have received a minimum of 6 standard cycles (75 mg/m2/cycle) of docetaxel, or a
total of >= 450 mg/m2.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
10. Patients, even if surgically sterilized (ie, status postvasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment
period and through 30 days after the last dose of study drug, or
- Agree to completely abstain from heterosexual intercourse.
11. Screening calculated ejection fraction of 50% by multiple gated acquisition (MUGA)
scan, or by echocardiogram (ECHO)
12. Stable medical condition
Exclusion criteria
1. Prior therapy with orteronel, ketoconazole, abiraterone, or aminoglutethimide.
2. Known hypersensitivity to compounds related to orteronel, to orteronel excipients, or prednisone, or to GnRH analogue.
3. Therapy with bicalutamide within 6 weeks of the first dose of study drug. All other antiandrogen therapy is excluded within 4 weeks prior to first dose of study drug.
4. Exposure to radioisotope therapy within 4 weeks of receiving the first dose of study drug; exposure to external beam radiation within 2 weeks of receiving the first dose of study drug.
5. Documented central nervous system metastases.
7. Current spinal cord compression, current bilateral hydronephrosis, or current bladder neck outlet obstruction.
8. Diagnosis of, or treatment for, another systemic malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and anyevidence of residual disease.
9. History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE version 4.02), or thromboembolic events within 6 months prior to first dose of study drug.
10. New York Heart Association Class III or IV heart failure.
11. ECG abnormalities of:
•*Q-wave infarction, unless identified 6 or more months prior to screening
•*QT interval > 460 msec
12. Uncontrolled hypertension despite appropriate medical therapy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-018662-23-NL |
| ClinicalTrials.gov | NCT01193257 |
| CCMO | NL33420.060.10 |