PREMIERE: Analyze the Predictive Value of Gene TMPRSS2-ETS in Response to Enzalutamide in Patients With Prostate Cancer
Study Details
Study Description
Brief Summary
Prostate cancer is the most common non-skin tumor diagnosed in men and the second leading cause of cancer death in men in Western countries.
Between 10-20% of patients are diagnosed at metastatic stage and about half of those diagnosed in early stages will develop metastases.
After the clinical benefit of mitoxantrone and the improved survival of 2-3 months provided by docetaxel in first line, the second search is driven to look for effective second lines treatments. In recent years, there are new drugs for the treatment of prostate cancer, revolutionizing the therapeutic sequence and survival.
Thus, androgen deprivation therapy, treatment of choice, induces an improvement of symptoms in approximately 70-80% of patients, but it is limited by the development of mechanisms of resistance to androgen deficiency. Docetaxel was the first chemotherapy drug to increase survival in patients with metastatic prostate cancer. The second cytotoxic drug approved in the second line treatment of metastatic CRPC has been cabazitaxel.
Enzalutamide improves survival in patients with metastatic CRPC who had progressed to chemotherapy and also in patients who had not received chemotherapy.
To date, there are no biomarkers available that allow us to identify which patients from a clinical or molecular view are those that will be able to benefit from the treatment options currently available. The presence of the TMPRSS2-ETS rearrangement has been shown to correlate with efficacy in clinical practice abiraterone.
There is scientific and preclinical background that makes one suspect that the molecular alteration may influence the same way enzalutamide antiandrogen activity, but it has not been determined to date.
The objective of this study is to determine whether the efficacy and safety of enzalutamide, when administered to patients with castration resistant prostate cancer prior to administration of docetaxel is influenced by the presence or absence of the fusion gene TMPRSS2- ETS.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Enzalutamide Enzalutamide 160 mg/day |
Drug: Enzalutamide
Enzalutamide 160 mg/day
|
Outcome Measures
Primary Outcome Measures
- PSA progression free survival [Up to 18 months]
Evaluate PSA progression (PCWG2 criteria) from date of patient inclusion until the date of first documented PSA progression or date of death from any cause, whichever came first, assessed up to 18 months.
Secondary Outcome Measures
- Number of individual events (hematologic events and not hematologic events) per patient [Up to 12 months]
Number of events per patient
- Time to PSA response [Up to 18 months]
Time from start of treatment to PSA progression (PCWG2 criteria)
- PSA response rate [Up to 18 months]
PSA response according to PCWG2 criteria, as % of patients with PSA response
- Radiologic progression free survival [Up to 18 months]
Radiologic progression free survival according RECIST 1.1 criteria, from date of patient inclusion until the date of first documented radiologic progression or date of death from any cause, whichever came first, assessed up to 18 months.
- Soft tissue response [Up to 18 months]
Soft tissue response according RECIST 1.1 criteria
- Time until the beginning of cytotoxic chemotherapy [Up to 18 months]
Time from date of patient inclusion until the date of the start of cytotoxic chemotherapy
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients aged 18 years and above, willing and able to provide written informed consent.
-
Prostate adenocarcinoma with histological or cytological confirmation without neuroendocrine differentiation nor small cell characteristics
-
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.
-
Testosterone serum level <= 1,73 nmol/L (50 ng/dL) in screening visit.
-
Patients under bisphosphonate therapy must have received stable doses for the last 4 weeks.
-
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 progression defined by PCWG2 criteria, with two or more new lesions in a scintigraphy
-
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.
-
Patients without previous cytotoxic chemotherapy for prostate cancer
-
Patients without previous abiraterone acetate therapy for prostate cancer - - 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.
-
Life expectancy of at least 6 months
-
Patient must be able to swallow the investigation product and to follow the protocol requirements.
-
Biomarker study informed consent
Exclusion Criteria:
-
Active infection or other medical condition which, in the opinion of the investigator, would preclude participation in this trial.
-
Known brain metastasis or leptomeningeal active involvement
-
Other malignancy in the last five years, except non-melanoma skin cancer treated and resolved.
-
Hematologic parameters: - Absolute neutrophil count <=1500/μL - Platelet count <100 000/μL - Haemoglobin < 5,6 mmol/L (9 g/dL)
-
Liver function: Serum bilirubin, SGPT/ALT or SGOT/AST > 2,5 x ULN
-
Renal function: Creatinine >177 μmol/L (2 mg/dL).
-
Serum albumin <30 g/L (3,0 g/dL)
-
History of epilepsy or other medical condition which could cause an epileptic crisis as syncope or transient ischemic attack in the last twelve months.
-
Clinically significant cardiovascular disease.
-
Known gastrointestinal (GI) disease that could interfere with the GI absorption.
-
Significant surgery within 4 weeks before enrollment.
-
Use of opioids to control cancer pain within 4 weeks before enrollment.
-
Radiation therapy for treatment of the primary tumor in the last 3 weeks before enrollment
-
Radiation therapy for treatment of metastases in the last two months
-
Radionuclide therapy for treatment of bone metastasis
-
Prior flutamide treatment within 4 weeks before enrollment
-
Bicalutamide or nilutamide therapy within 6 weeks before enrollment
-
5-a reductase inhibitors, estrogen o cyproterone therapy within 4 weeks before enrollment
-
Biologic therapy or other antitumoral drugs for the treatment of CRPC in the last 4 weeks
-
History of cancer progression with ketoconazole
-
Prior therapy or enrollment in a trial with an investigational product which blocks androgen synthesis (abiraterone, TAK-700, TAK-683, TAK-448) or blocks androgen receptors (ARN507, BMS 641988).
-
Included in a previous trial with enzalutamide (MDV3100).
-
Administration of an investigational drug in the last 4 weeks before enrollment
-
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
-
Hereditary fructose intolerance
-
Any condition which, in the opinion of the investigator, would preclude participation in this trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitari Germans Trias I Pujol de Badalona | Badalona | Barcelona | Spain | 08916 |
| 2 | Hospital Universitari Son Espases | Palma de Mallorca | Islas Baleares | Spain | 07120 |
| 3 | Hospital Clinic I Provincial de Barcelona | Barcelona | Spain | 08036 | |
| 4 | Hospital Parc Taulí | Barcelona | Spain | ||
| 5 | Complejo Hospitalario Regional Reina Sofía | Córdoba | Spain | 14004 | |
| 6 | Complejo Asistencial Universitario de Leon | León | Spain | 24080 | |
| 7 | Hospital Universitario Lucus Augusti | Lugo | Spain | 27003 | |
| 8 | Hospital Ramón Y Cajal | Madrid | Spain | 28034 | |
| 9 | Hospital Clínico San Carlos | Madrid | Spain | 28040 | |
| 10 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 11 | Hospital General Universitario J.M. Morales Meseguer | Murcia | Spain | 30008 | |
| 12 | Complejo Hospitalario de Especialidades Virgen de La Victoria | Málaga | Spain | 29010 | |
| 13 | Complexo Hospitalario Universitario de Ourense | Ourense | Spain | 32005 | |
| 14 | Complejo Hospitalario Regional Virgen Del Rocio | Sevilla | Spain | 41013 | |
| 15 | Fundación Instituto Valenciano de Oncologia | Valencia | Spain | 46009 | |
| 16 | Hospital Universitario Miguel Servet | Zaragoza | Spain | 50009 |
Sponsors and Collaborators
- Spanish Oncology Genito-Urinary Group
- Astellas Pharma Inc
- Apices Soluciones S.L.
Investigators
- Study Director: Enrique Grande, MD, Hospital Universitario Ramon y Cajal
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SOG-MIE-2014-04
- 2014-003192-28