NCT02288936: PREMIERE

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

Completed Phase 2 Last updated 24 September 2019

What this trial tests

Phase 2 trial testing Enzalutamide in Hormone-refractory Prostate Cancer in 98 participants. Completed in 22 July 2019.

Timeline

5 February 2015

Primary endpoint
22 July 2019

22 July 2019

Quick facts

Lead sponsor	Spanish Oncology Genito-Urinary Group
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	98
Start date	5 February 2015
Primary completion	22 July 2019
Estimated completion	22 July 2019
Sites	16 locations across Spain

Drugs / interventions tested

• Enzalutamide (enzalutamide) — full drug profile →

Conditions studied

• Hormone-refractory Prostate Cancer — all drugs for Hormone-refractory Prostate Cancer →

Sponsor

Spanish Oncology Genito-Urinary Group — full company profile →

Who can join

18 and older, male only, with Hormone-refractory Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. 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.
   Conteduca V, Wetterskog D, Sharabiani MTA, Grande E, et al · · 2017 · cited 204× · PMID 28472366 · DOI 10.1093/annonc/mdx155
2. Genome-wide plasma DNA methylation features of metastatic prostate cancer.
   Wu A, Cremaschi P, Wetterskog D, Conteduca V, et al · · 2020 · cited 84× · PMID 32149736 · DOI 10.1172/jci130887
3. New Prognostic Biomarkers in Metastatic Castration-Resistant Prostate Cancer.
   Conteduca V, Mosca A, Brighi N, de Giorgi U, et al · · 2021 · cited 38× · PMID 33478015 · DOI 10.3390/cells10010193
4. Clinically relevant fusion oncogenes: detection and practical implications.
   Sorokin M, Rabushko E, Rozenberg JM, Mohammad T, et al · · 2022 · cited 25× · PMID 36601633 · DOI 10.1177/17588359221144108
5. Plasma Androgen Receptor Copy Number Status at Emergence of Metastatic Castration-Resistant Prostate Cancer: A Pooled Multicohort Analysis.
   Jayaram A, Wingate A, Wetterskog D, Conteduca V, et al · · 2019 · cited 21× · PMID 32923850 · DOI 10.1200/po.19.00123
6. Plasma Androgen Receptor in Prostate Cancer.
   Conteduca V, Gurioli G, Brighi N, Lolli C, et al · · 2019 · cited 13× · PMID 31689899 · DOI 10.3390/cancers11111719
7. A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide.
   Fernandez-Perez MP, Perez-Navarro E, Alonso-Gordoa T, Conteduca V, et al · · 2023 · cited 8× · PMID 36564933 · DOI 10.1002/pros.24469
8. Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer.
   Perez-Navarro E, Conteduca V, Funes JM, Dominguez JI, et al · · 2024 · cited 2× · PMID 39061175 · DOI 10.3390/cancers16142535