Analyze the predictive value of gene TMPRSS2-ETS in response to enzalutamide in patients with prostate cancer
- Conditions
- MedDRA version: 17.1 Level: PT Classification code 10062904 Term: Hormone-refractory prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Metastatic castration-resistant prostate cancer no previously treated with chemotherapyTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003192-28-ES
- Lead Sponsor
- SOGUG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 98
1. Patients aged 18 years and above, willing and able to provide written informed consent.
2. Prostate adenocarcinoma with histological or cytological confirmation without neuroendocrine differentiation nor small cell characteristics
3. Androgen deprivation therapy with GnRH analogs or bilateral orchiectomy (pharmacological or surgical castration). Patients without bilateral orchiectomy must follow a GnRH analog therapy during the trial.
4. Testosterone serum level <= 1,73 nmol/L (50 ng/dL) in screening visit.
5. Patients under bisphosphonate therapy must have received stable doses for the last 4 weeks.
6. Progression disease at inclusion, defined by one or more of the following three criteria during androgen deprivation therapy (according with the criterion nº 3):
- PSA progression defined as two elevation of the PSA serum level with >=1 week between each measure. Patients who have received an antiandrogen must present disease progression (>=4 weeks since the last dose of flutamide or >=6 weeks since the last dose of bicalutamide or nilutamide). PSA value in screening visit must be >=2 µg/L (2 ng/mL).
- Soft tissue progression defined by RECIST 1.1 criteria
- Bone lesion progresión defined by PCWG2 criteria, with two or more new lesions in a scintigraphy
7. Metastatic disease with bone lesions detected by scintigraphy, or measurable soft tissue lesions by CT/MR. Patients with ganglionar disease will be suitable if they have at least one ganglionar lesion with smallest diameter > 2,5 cm.
8. Patients without previous cytotoxic chemotherapy for prostate cancer
9. Patients without previous abiraterone acetate therapy for prostate cancer
10. Asymptomatic patient or mild symptomatic about prostate cancer, (answer in the question nº 3 of the Brief Pain Inventory Short From < 4)
11. ECOG = 0-1.
12. Life expectancy of at least 6 months
13. Patient must be able to swallow the investigation product and to follow the protocol requirements.
14. Biomarker study informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 68
1. Active infection or other medical condition which, in the opinion of the investigator, would preclude participation in this trial.
2. Known brain metástasis or leptomeningeal active involvement
3. Other malignancy in the last five years, except non-melanoma skin cancer treated and resolved.
4. Hematologic parameters:
- Absolute neutrophil count <=1500/µL
- Platelet count <100 000/µL
- Haemoglobin < 5,6 mmol/L (9 g/dL)
5. Liver function: Serum bilirrubin, ALT or AST > 2,5 x ULN
6. Renal function: Creatinine >177 µmol/L (2 mg/dL).
7. Serum albumin <30 g/L (3,0 g/dL)
8. History of epilepsy or other medical condition which could cause an epileptic crisis as syncope or transient ischemic attack in the last twelve months.
9. Clinically significant cardiovascular disease, including:
- Myocardial infarction in the last 6 months
- Severe or unstable angina in the last 3 months
- New York Heart Association (NYHA) Class II-IV heart disease unless cardiac ejection fraction measurement of >=45% at 3 previous months
- History of clinically significant ventricular arrhythmia
- History of second degree AV bock or third degree AV block without permanent pacemaker
- Hypotension determined by a baseline systolic blood pressure < 86 mmHg
- Bradycardia detemined by heart rate < 50 BPM in baseline ECG
- Uncontrolled hypertension (systolic BP > 170 mmHg or diastolic BP > 105 mmHg).
10. Known gastrointestinal (GI) disease that could interfere with the GI absorption.
11. Significant surgery within 4 weeks before enrollment.
12. Use of opioids to control cancer pain within 4 weeks before enrollment.
13. Radiation therapy for treatment of the primary tumor in the last 3 weeks before enrollment
14. Radiation therapy for treatment of metastases in the last two months
15. Radionuclide therapy for treatment of bone metastasis
16. Prior flutamide treatment within 4 weeks before enrollment
17. Bicalutamide or nilutamide therapy within 6 weeks before enrollment
18. 5-a reductase inhibitors, estrogen o ciproterone therapy within 4 weeks before enrollment
19. Biologic therapy or other antitumoral drugs for the treatment of CRPC in the last 4 weeks
20. History of cancer progression with ketokonazol
21. Prior therapy or enrollment in a trial with an investigational product which blocks androgen synthesis (abiraterona, TAK-700, TAK-683, TAK-448) or blocks androgen receptors (ARN507, BMS 641988).
22. Included in a previous trial with enzalutamide (MDV3100).
23. Administration of an investigational drug in the last 4 weeks before enrollment
24. Use of phytotherapy products which hormonal activity against prostate cancer or which reduce PSA levels, or systemic corticosteroids in a dose greater than the equivalent of prednisone 10mg/day, within 4 weeks before enrollment
25. Hereditary fructose intolerance
26. Any condition which, in the opinion of the investigator, would preclude participation
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: PSA progression free survival (PCWG2 criteria) depending on the presence of TMPRSS2-ETS fusion gene rearrangements;<br> Secondary Objective: Assessment of the raliationship between the presence of TMPRSS2-ETS fusión gene rearrangements with:<br> - Time to PSA response<br> - PSA response rate<br> - Radiologic progression free survival according to RECIST v1.1 criteria.<br> - Overall soft tissue response rate<br> - Time untill the beginning of cytotoxic chemotherapy<br> - Safety of enzalutamide treatment<br> - CTC conversión rate<br> ;Primary end point(s): PSA progression free survival;Timepoint(s) of evaluation of this end point: Every 4 weeks
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): - Time to PSA response<br> - PSA response rate<br> - Radiologíc progression free survival according RECIST 1.1 criteria<br> - Soft tissue response according RECIST 1.1 criteria.<br> - Time until the beginning of cytotoxic chemotherapy<br> - Safety profile according to NCI-CTCAE v.4.03<br> - CTC conversion rate<br> ;<br> Timepoint(s) of evaluation of this end point: - Every 4 weeks<br> - Every 4 weeks<br> - Every 12 weeks<br> - Every 12 weeks<br> - Every 12 weeks<br> - Every 4 weeks<br> - At disease progression<br>