Phase II Multicenter Study to Analyze the Predictive Value of Fusion Gene TMPRSS2-ETS in Response to Enzalutamide in Patients With Metastatic CRPC no Previously Treated With Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Enzalutamide
- Conditions
- Hormone-refractory Prostate Cancer
- Sponsor
- Spanish Oncology Genito-Urinary Group
- Enrollment
- 98
- Locations
- 16
- Primary Endpoint
- PSA progression free survival
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility 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)
- •Life expectancy of at least 6 months
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.
Arms & Interventions
Enzalutamide
Enzalutamide 160 mg/day
Intervention: Enzalutamide
Outcomes
Primary Outcomes
PSA progression free survival
Time Frame: 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 Outcomes
- Number of individual events (hematologic events and not hematologic events) per patient(Up to 12 months)
- Time to PSA response(Up to 18 months)
- Soft tissue response(Up to 18 months)
- Time until the beginning of cytotoxic chemotherapy(Up to 18 months)
- PSA response rate(Up to 18 months)
- Radiologic progression free survival(Up to 18 months)