To determine if orteronel plus prednisone improves radiographic progression-freesurvival (rPFS)To determine if orteronel plus prednisone improves overall survival (OS)
ID
Source
Brief title
Condition
- Reproductive neoplasms male benign
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Objectives:
To determine if orteronel plus prednisone improves radiographic progression-free
survival (rPFS)
To determine if orteronel plus prednisone improves overall survival (OS)
Secondary outcome
Key Secondary Objectives:
To determine if orteronel plus prednisone improves 50% prostate-specific
antigen (PSA)
response at 12 weeks
To evaluate changes in circulating tumor cell (CTC) counts
To evaluate whether orteronel improves time to pain progression
Other Secondary Objectives:
To assess the safety of orteronel plus prednisone
To determine if orteronel plus prednisone increases the time to radiographic
disease
progression or skeletal-related event (SRE)
To determine if orteronel plus prednisone decreases frequency of SREs
To determine if orteronel plus prednisone increases 90% PSA response and best
PSA
response
To determine if orteronel plus prednisone increases time to PSA progression
To evaluate if orteronel plus prednisone improves time to docetaxel chemotherapy
To measure the time to subsequent antineoplastic therapy
To determine tumor response rate and duration of response in patients with tumor
lesions that are measurable by the Response Evaluation Criteria in Solid Tumors
(RECIST 1.1)
To assess global health status as measured by the European Organization for
Research
and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30), a
patientreported
outcome (PRO) instrument
To collect blood orteronel concentration data for use in a future integrated
pharmacokinetic (PK) analysis
Background summary
Orteronel 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
radiographic progression-free survival (rPFS) and overall survival (OS)
in men with progressive metastatic castration-resistant prostate cancer (mCRPC)
that has not previously been treated with chemotherapy for metastatic disease
(chemotherapy naïve).
Study objective
To determine if orteronel plus prednisone improves radiographic progression-free
survival (rPFS)
To determine if orteronel plus prednisone improves overall survival (OS)
Study design
This is a randomized, double-blind, multicenter, phase 3 study evaluating
orteronel plus prednisone compared with placebo plus prednisone in the
treatment of men with progressive, chemotherapy-naïve, metastatic,
castration-resistant prostate cancer (mCRPC). Patients in the 2 treatment
groups will receive blinded orteronel (or placebo) in addition to open-label
prednisone and gonadotropin-releasing hormone (GnRH) analogue therapy.
Patients who have undergone orchiectomy and have a testosterone concentration
of < 50 ng/dL may participate in the study without prior or ongoing concomitant
GnRH analogue treatment. Two formal interim analyses are 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 orteronel, or 2)
discontinue orteronel but have not yet experienced disease progression.
Patients will discontinue scheduled study visits if they experience disease
progression and decide to discontinue orteronel. Patients may remain on
orteronel 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 Predison (oral)
Study burden and risks
Extra procedures: MUGA/ECHO (Screening, Cyclus (C) 4, C7, C13, Q6C, EOT); ECG
(Scr, C2, C7, C13, Q12C, 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).
Landsdown Street 40
Cambridge MA USA 02139
US
Landsdown Street 40
Cambridge MA USA 02139
US
Listed location countries
Age
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be enrolled in the study:
1. Male patients 18 years or older.
2. Voluntary written consent, given before performance of any study related procedure not part of standard medical care, and with the understanding that consent may be withdrawn at any time without prejudice to future medical care.
3. Adenocarcinoma of the prostate either histologically or cytologically confirmed.
4. Metastatic disease radiographically documented by CT/MRI or bone scan.
5. Progressive disease based on PSA and/or radiographic criteria, defined as 1 or more of the following:
• Radiographic disease progression based on RECIST 1.1 (refer to Section 15.1 of protocol) in patients with measurable soft tissue lesions. For patients with bone disease, progression will be assessed following recommendations by the Prostate Cancer Working Group (PCWG2; refer to Section 15.1); appearance of 2 or more new lesions on bone scan, confirmed, if necessary, by other imaging modalities (such as CT scan or MRI), if results of the bone scans are ambiguous.
• PSA progression is defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart and confirmed by a third. If the third measurement is not greater than the second measurement, then a fourth measurement must be taken and must be greater than the second measurement for the patient to be eligible for randomization in the study. Furthermore, the confirmatory PSA measurement (ie, the third or, if applicable, fourth PSA measurement) must be >= 2 ng/mL. Notes: Determination of PSA progression can be based on results from a local laboratory. The PSA value obtained from the central laboratory during the screening process does not have to be used in the determination of PSA progression, but that value should be at least greater than the first PSA used for determination of PSA progression. If a patient has received prior antiandrogen therapy (eg, bicalutamide, MDV-3100), PSA progression must be evident and documented after discontinuation of antiandrogen therapy.
6. Prior surgical castration or concurrent use of an agent for medical castration (eg, GnRH analogue) with testosterone at screening < 50 ng/dL.
7. Either absence of pain or pain, regardless of cause, not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to randomization.
8. Screening PSA >= 2 ng/mL. (Screening PSA value must be obtained from the central laboratory.)
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Section 15.2.2).
10. Screening clinical laboratory values as specified below:
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5 X the upper limit of normal (ULN).
• Total bilirubin <= 1.5 X ULN.
• Estimated creatinine clearance using the Cockcroft-Gault formula must be > 40 mL/minute (see Section 15.4).
• Absolute neutrophil count (ANC) >=1500/µL and platelet count >= 100,000/µL.
11. Patients, even if surgically sterilized (ie, status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and for 4 Months after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual
lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal,
postovulation methods for the female partner] and withdrawal are not acceptable
methods of contraception.)
12. Screening calculated ejection fraction of >= 50% by multiple gated acquisition (MUGA) scan, or by echocardiogram (ECHO). (The same modality should be used for a patient throughout the study.)
13. Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 28 days prior to randomization, and otherwise noted in other inclusion/exclusion criteria.
14. Life expectancy of 12 months or more based on general health and prostate cancer disease status as judged by the investigator.
Exclusion criteria
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
1. Prior therapy with orteronel, ketoconazole, aminoglutethimide, or abiraterone.
2. Known hypersensitivity to compounds related to orteronel, orteronel excipients, prednisone, or GnRH analogue.
3. All antiandrogen therapy (including bicalutamide) is excluded within 4 weeks prior to first dose of study drug. Any other therapies for prostate cancer, other than GnRH analogue therapy, such as progesterone, medroxyprogesterone, progestins (megesterol), or 5-alpha reductase inhibitors (eg, finasteride or dutasteride), must be discontinued 2 weeks before the first dose of study drug.
4. Continuous daily use of oral prednisone, oral dexamethasone, or other systemic corticosteroids for more than 14 days within 3 months prior to screening (inhaled, nasal, and local steroids are allowed [eg, joint injection]).
5. Prior chemotherapy for PC, with the exception of neoadjuvant/adjuvant therapy as part of initial primary treatment for local disease that was completed 2 or more years prior to screening.
6. Exposure to radioisotope therapy within 4 weeks of receiving the first dose of study drug; exposure to external beam radiation within 4 weeks of receiving the first dose of study drug.
7. Documented central nervous system metastases.
8. Treatment with any investigational compound within 30 days prior to the first dose of study drug or ongoing active participation in another experimental trial related to the treatment of PC. (Patients who are in long-term follow-up following active treatment in other trials are eligible.)
9. Current spinal cord compression, current bilateral hydronephrosis, or current bladder neck outlet obstruction. Note: Patients with definitive local therapy for urinary tract obstruction, eg with stents, may be eligible after a review by the study project clinician.
10. 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 have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
11. History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.02)(77), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within 6 months prior to first dose of study drug. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
12. New York Heart Association Class III or IV heart failure (see Section 15.5 of protocol).
13. ECG abnormalities of:
• Q-wave infarction, unless identified 6 or more months prior to screening
• QTc interval > 460 msec
14. Uncontrolled hypertension despite appropriate medical therapy (blood pressure [BP] of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the Screening visit). Note: Patients may be rescreened after adjustments of antihypertensive medications.
15. Known human immunodeficiency virus (HIV) infection, active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator*s opinion, potentially interfere with participation in this study. Patients will be tested for hepatitis B or C or HIV infection during screening if they are considered by the investigator to be at higher risk for these infections and have not been previously tested, or if testing is required by the independent ethics committee or institutional review board.
16. Uncontrolled nausea, vomiting, or diarrhea despite appropriate medical therapy.
17. Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of orteronel, including difficulty swallowing tablets.
18. Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel.
19. Those patients whose prostate cancer is confined to just the prostate bed or immediate adjacent tissue.
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 | EUCTR2010-018661-35-NL |
ClinicalTrials.gov | NCT01193244 |
CCMO | NL33419.060.10 |