Analyze the Predictive Value of Gene TMPRSS2-ETS in Response to Enzalutamide in Patients With Prostate Cancer

NCT02288936 | Completed Phase 2

• 2 other identifiers: SOG-MIE-2014-042014-003192-28
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 16

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.

Conditions

Hormone-refractory Prostate Cancer

Keywords

Hormone-refractory prostate cancer; Enzalutamide; TMPRSS2-ETS fusion gene

Outcome Measures

Primary Outcomes (1)

• PSA progression free survival

  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.

  Up to 18 months

Secondary Outcomes (6)

• Number of individual events (hematologic events and not hematologic events) per patient

  Up to 12 months

• Time to PSA response

  Up to 18 months

• PSA response rate

  Up to 18 months

• Radiologic progression free survival

  Up to 18 months

• Soft tissue response

  Up to 18 months

Study Arms (1)

Enzalutamide

EXPERIMENTAL

Enzalutamide 160 mg/day

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Enzalutamide 160 mg/day

Enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spanish Oncology Genito-Urinary Group: lead
• Astellas Pharma Inc: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (16)

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Hospital Universitari Germans Trias I Pujol de Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital Clinic I Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Parc Taulí

Barcelona, Spain

Location

Complejo Hospitalario Regional Reina Sofía

Córdoba, 14004, Spain

Location

Complejo Asistencial Universitario de Leon

León, 24080, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Ramón Y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Complejo Hospitalario de Especialidades Virgen de La Victoria

Málaga, 29010, Spain

Location

Hospital General Universitario J.M. Morales Meseguer

Murcia, 30008, Spain

Location

Complexo Hospitalario Universitario de Ourense

Ourense, 32005, Spain

Location

Complejo Hospitalario Regional Virgen Del Rocio

Seville, 41013, Spain

Location

Fundación Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (3)

• Jayaram A, Wingate A, Wetterskog D, Conteduca V, Khalaf D, Sharabiani MTA, Calabro F, Barwell L, Feyerabend S, Grande E, Martinez-Carrasco A, Font A, Berruti A, Sternberg CN, Jones R, Lefresne F, Lahaye M, Thomas S, Joshi S, Shen D, Ricci D, Gormley M, Merseburger AS, Tombal B, Annala M, Chi KN, De Giorgi U, Gonzalez-Billalabeitia E, Wyatt AW, Attard G. Plasma Androgen Receptor Copy Number Status at Emergence of Metastatic Castration-Resistant Prostate Cancer: A Pooled Multicohort Analysis. JCO Precis Oncol. 2019 Sep 24;3:PO.19.00123. doi: 10.1200/PO.19.00123. eCollection 2019.

  PMID: 32923850 DERIVED

• Wu A, Cremaschi P, Wetterskog D, Conteduca V, Franceschini GM, Kleftogiannis D, Jayaram A, Sandhu S, Wong SQ, Benelli M, Salvi S, Gurioli G, Feber A, Pereira MB, Wingate AM, Gonzalez-Billalebeitia E, De Giorgi U, Demichelis F, Lise S, Attard G. Genome-wide plasma DNA methylation features of metastatic prostate cancer. J Clin Invest. 2020 Apr 1;130(4):1991-2000. doi: 10.1172/JCI130887.

  PMID: 32149736 DERIVED

• Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, Fernandez-Perez MP, Jayaram A, Salvi S, Castellano D, Romanel A, Lolli C, Casadio V, Gurioli G, Amadori D, Font A, Vazquez-Estevez S, Gonzalez Del Alba A, Mellado B, Fernandez-Calvo O, Mendez-Vidal MJ, Climent MA, Duran I, Gallardo E, Rodriguez A, Santander C, Saez MI, Puente J, Gasi Tandefelt D, Wingate A, Dearnaley D; PREMIERE Collaborators; Spanish Oncology Genitourinary Group; Demichelis F, De Giorgi U, Gonzalez-Billalabeitia E, Attard G. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Ann Oncol. 2017 Jul 1;28(7):1508-1516. doi: 10.1093/annonc/mdx155.

  PMID: 28472366 DERIVED

MeSH Terms

Interventions

enzalutamide

Study Officials

• Enrique Grande, MD

  Hospital Universitario Ramon y Cajal

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: November 13, 2014
• Study Start: February 5, 2015
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: September 24, 2019

Record last verified: 2019-09

Locations

ES (16)