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Hormone-refractory Prostate CancerPhase 2PREMIERENCT02288936

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

A Phase 2 study testing Enzalutamide in people with Hormone-refractory Prostate Cancer, run by Spanish Oncology Genito-Urinary Group at 16 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Hormone-refractory Prostate Cancer
What is being tested?
Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
16 sitesSpain
Study dates
5 Feb 2015to 22 Jul 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Spain16 sites

  • Hospital Universitari Germans Trias I Pujol de Badalona

    Badalona, Barcelona, 08916

  • Hospital Clinic I Provincial de Barcelona

    Barcelona, 08036

  • Hospital Parc Taulí

    Barcelona

  • Complejo Hospitalario Regional Reina Sofía

    Córdoba, 14004

  • Complejo Asistencial Universitario de Leon

    León, 24080

  • Hospital Universitario Lucus Augusti

    Lugo, 27003

  • Hospital Ramón Y Cajal

    Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Complejo Hospitalario de Especialidades Virgen de La Victoria

    Málaga, 29010

  • Hospital General Universitario J.M. Morales Meseguer

    Murcia, 30008

  • Complexo Hospitalario Universitario de Ourense

    Ourense, 32005

  • Hospital Universitari Son Espases

    Palma de Mallorca, Balearic Islands, 07120

  • Complejo Hospitalario Regional Virgen Del Rocio

    Seville, 41013

  • Fundación Instituto Valenciano de Oncologia

    Valencia, 46009

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

About this study

Official title: 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

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.

Read more

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.

Being tested
Enzalutamide
Keywords
Hormone-refractory prostate cancer, Enzalutamide, TMPRSS2-ETS fusion gene

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02288936
Study groupRoleWhat they receive
EnzalutamideExperimentalEnzalutamide 160 mg/day
Receives: Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 18 months

Secondary outcomes (6)

  1. Number of individual events (hematologic events and not hematologic events) per patient

    Number of events per patient

    Measured: Up to 12 months

  2. Time to PSA response

    Time from start of treatment to PSA progression (PCWG2 criteria)

    Measured: Up to 18 months

  3. PSA response rate

    PSA response according to PCWG2 criteria, as % of patients with PSA response

    Measured: Up to 18 months

  4. Radiologic progression free survival

    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.

    Measured: Up to 18 months

  5. Soft tissue response

    Soft tissue response according RECIST 1.1 criteria

    Measured: Up to 18 months

  6. Time until the beginning of cytotoxic chemotherapy

    Time from date of patient inclusion until the date of the start of cytotoxic chemotherapy

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2014 (estimated)
  2. Study start5 Feb 2015
  3. Primary completion22 Jul 2019
  4. Study completion22 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02288936
Sponsor's protocol ID
SOG-MIE-2014-04
Other IDs
2014-003192-28, 2014
Acronym
PREMIERE
Status last verified
Sep 2019
First submitted
28 Oct 2014
Last updated
24 Sep 2019
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 32923850

  • 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.

    PubMed 32149736

  • 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.

    PubMed 28472366

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Enzalutamide in people with Hormone-refractory Prostate Cancer, run by Spanish Oncology Genito-Urinary Group at 16 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA progression free survival (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02288936, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2019.

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