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Prostate CancerPhase 2BonEnzaNCT03336983

Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients

A Phase 2 study testing Zoledronic Acid and Enzalutamide in people with Prostate Cancer and Bone Metastases, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.

Completed

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

Official record
Search all trials

Trial summary

This study was undertaken to evaluate bone response in metastatic prostate cancer patients treated with Enzalutamide with or without Zoledronic Acid in combination with luteinizing hormone-releasing hormone (LHRH) analogue with the use of Whole Boby (WB) DW-MRI. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer, Bone Metastases
What is being tested?
Zoledronic Acid and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
126 participants
Where
1 siteItaly
Study dates
1 Dec 2017to 1 Apr 2023
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

  • Histological diagnosis of prostate carcinoma,
  • Age > 18 years,
  • Metastatic disease documented as the presence of bone lesions on bone scan associated or not to soft tissue lesions measurable at computed tomography (CT) scan or Magnetic Resonance Imaging (MRI),
  • No previous hormone or chemotherapeutic treatments given for prostate carcinoma (patients that are receiving LHRH-A therapy for less than 4 months are admitted),
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1,
  • Expected life expectancy ≥ 6 months,
  • Subject capable to swallow the Study's medication and to comply with the Study's requirements,
  • Signed informed consent.

Who cannot join

  • Presence of active serious disease, active infection or co-comorbidity that may prevent the study enrollment make (at the discretion of the clinical Investigator),
  • Known or suspected brain metastases or active leptomeningeal dissemination,
  • History of other malignant neoplasm during the previous 5 years, different from the non-melanoma skin carcinoma,
  • Absolute Neutrophil Count (ANC) < 1.500/µL, platelet < 100.000/µL, or hemoglobin < 5,6 mmol/L (< 9 g/dL) at Screening Visit (notably: patients must not receive neither any growth factor during the previous 7 days nor any blood transfusion during the 28 days preceding the hematology sampling performed at Screening),
  • Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2,5 x upper limit of normal (ULN) at Screening Visit,
  • Creatinine > 177 µmol/L (> 2 mg/dL) at Screening Visit,
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  • Albumin ≤ 30 g/L (≤ 3,0 g/dL) at Screening Visit,
  • History of seizures or any other seizure-predisposed pathology; history of loss of consciousness or transitory ischaemic attack during the 12 months preceding the Screening visit,
  • Clinically significant cardiovascular disease including:
  • myocardial infarction (6 months preceding the screening)
  • uncontrolled angina (3 months preceding the screening)
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥ 45%;
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
  • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
  • Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mmHg) at the Screening visit;
  • Bradycardia as indicated by a heart rate of < 50 beats per minute on the Screening ECG;
  • Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the Screening visit;
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
  • Major surgery within 4 weeks of enrollment (Day 1 Visit);
  • Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment (Day 1 visit);
  • Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease Prostate-specific antigen (PSA) levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within four weeks of enrollment (Day 1 visit);
  • Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Azienda Ospedaliera Spedali Civili di Brescia

    Brescia, 25123

Other trials in Italy

About this study

Official title: Bone Response After Luteinizing Hormone-releasing Hormone Analogue and Enzalutamide +/- Zoledronic Acid in Prostate Cancer Patients With Hormone Sensitive Metastatic Bone Disease: a Prospective, Phase II, Randomized, Multicenter Study

This study was undertaken to evaluate bone response in metastatic prostate cancer patients treated with Enzalutamide with or without Zoledronic Acid in combination with luteinizing hormone-releasing hormone (LHRH) analogue with the use of Whole Boby (WB) DW-MRI.

Read the detailed description

Most men with fatal prostate cancer develop bone metastases and bone is often the dominant or the only site of metastatic disease. Bone metastases are an important cause of morbidity since they are associated with skeletal related events (SREs) including pathologic fractures, spinal cord compression, and need for surgery or radiation therapy to bone. Osteoclast-mediated bone destruction is the key pathologic mechanism for SREs in prostate cancer and other malignancies. Zoledronic acid (ZA) is a potent inhibitors of osteoclast-mediated bone resorption. ZA has demonstrated to be effective in preventing SREs in patients with castrate resistant disease; however, its efficacy in hormone naïve disease is uncertain.

In the last few years new drugs targeting directly the androgen receptor such as Enzalutamide have shown to be very effective in terms of survival prolongation in the management of castration resistant disease and the efficacy in hormone naïve patients is currently under investigation. Interestingly, the results of a large scale, prospective, randomized clinical trial have shown that Enzalutamide administration is also associated with a reduction in the risk of SREs and this raises the question of the usefulness of the addition of bone resorption inhibitors to Enzalutamide.

The evaluation of bone response of antineoplastic therapies has always been difficult in metastatic bone prostate cancer patients due to their osteoblastic nature. Whole body diffusion-weighted (DW) MRI has been recently proposed as new imaging tool for grading treatment response in patients with skeletal metastases from prostate cancer. According to the literature data DW images can allow the identification of bone marrow infiltration and tumor necrosis induced by treatment. In addition, this technique allows to monitor the bone marrow restoration. This, this technique was selected to evaluate bone response in metastatic prostate cancer patients treated with Enzalutamide with or without Zoledronic Acid in combination with LHRH-A.

Moreover, since androgen-receptor isoform encoded by splice variant 7 (AR-V7) is an androgens' receptor variant that could have a potential clinical utility as a prognostic factor and predictive marker of therapy response, an ancillary study will be conducted to evaluate ARV7 expression in Circulating Tumor Cells (CTC).

Keywords
prostate cancer, bone metastasis, enzalutamide, zoledronic acid
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • Zoledronic AcidDrug

    Also called Zoledronate

    Prostate cancer patients with hormone sensitive metastatic bone disease will be treated with LHRH-A + Enzalutamide in the presence or absence of Zoledronic Acid

  • EnzalutamideDrug

    Also called Xtandi

    Patients from both arms will be treated with LHRH-A + Enzalutamide

Study groups in NCT03336983
Study groupRoleWhat they receive
LHRH-A + EnzalutamideOtherProstate cancer patients with hormone sensitive metastatic bone disease will be treated with LHRH-A + Enzalutamide until patient's progression, consent withdrawal or unacceptable toxicity
Receives: Drug: Enzalutamide
LHRH-A + Enzalutamide + Zoledronic AcidExperimentalProstate cancer patients with hormone sensitive metastatic bone disease will be treated with LHRH-A + Enzalutamide + Zoledronic Acid until patient's progression, consent withdrawal or unacceptable toxicity
Receives: Drug: Zoledronic Acid; Drug: Enzalutamide

What is being measured

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

  1. Evaluation of change in bone response after 6 and 12 months of treatment compared to baseline

    Whole-body Diffusion MRI

    Measured: Exam will be performed at baseline and after 6 and 12 months of treatment

Secondary outcomes (7)

  1. Evaluation of bone repair

    CT Scan

    Measured: Screening visit; 12 months of treatment

  2. Changes in bone mineral density after 18 months of treatment compared to baseline

    Dual energy x-ray absorptiometry (DEXA Scan)

    Measured: Screening visit; 18 months of treatment

  3. Functional Assessment of Cancer Therapy-Prostate

    Functional Assessment of Cancer Therapy-Prostate (FACT- P) Questionnaire will be collected from patients.It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global Qquality of Life (QoL) score.

    Measured: Monthly until end of treatment (18 months)

  4. Brief Pain Inventory-Short Form Questionnaire

    Brief Pain Inventory-Short Form (BPI-SF) Questionnaire will be collected from patients.In particular, a 0-10 numerical rating scale was used to measure pain severity items where 0=no pain and 10=pain as bad as you can imagine or with 0=pain did not interfere with my normal life and 10=pain interferes ompletely. A question about the percentage and duration of pain relief was also included.

    Measured: Monthly until end of treatment (18 months)

  5. Weight evaluation

    Evaluation of patient weight expressed in kg after 18 months of treatment compared to baseline

    Measured: Screening visit; 18 months of treatment

  6. C-terminal telopeptide analysis

    C-terminal telopeptide analysis (CTX, ng/ml) evaluation on peripheral blood samples

    Measured: Screening visit; 2, 4, 6, 9, 12, 18 months of treatment

  7. Bone alkaline phosphatase analysis

    Bone alkaline phosphatase analysis (U/uL) evaluation on peripheral blood samples

    Measured: Screening visit; 2, 4, 6, 9, 12, 18 months of treatment

Timeline

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

  1. First posted8 Nov 2017
  2. Study start1 Dec 2017
  3. Primary completion30 Jun 2022
  4. Study completion1 Apr 2023

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
Randomised
Intervention model
Parallel groups
Model description
prostate cancer patients with hormone sensitive metastatic bone disease
Masking
None (open label)
Enrolment
126 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03336983
Sponsor's protocol ID
ASCB-ONCO-2336-2017
Other IDs
2017-000305-21, 2017
Acronym
BonEnza
Status last verified
Jul 2024
First submitted
23 Oct 2017
Last updated
1 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schmidt GP, Reiser MF, Baur-Melnyk A. Whole-body MRI for the staging and follow-up of patients with metastasis. Eur J Radiol. 2009 Jun;70(3):393-400. doi: 10.1016/j.ejrad.2009.03.045. Epub 2009 May 19.

    PubMed 19457631

  • Koh DM, Blackledge M, Padhani AR, Takahara T, Kwee TC, Leach MO, Collins DJ. Whole-body diffusion-weighted MRI: tips, tricks, and pitfalls. AJR Am J Roentgenol. 2012 Aug;199(2):252-62. doi: 10.2214/AJR.11.7866.

    PubMed 22826385

  • Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, Hauke RJ, Monk JP, Saylor P, Bhoopalam N, Saad F, Sanford B, Kelly WK, Morris M, Small EJ. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014 Apr 10;32(11):1143-50. doi: 10.1200/JCO.2013.51.6500. Epub 2014 Mar 3.

    PubMed 24590644

  • Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.

    PubMed 22894553

  • Saad F, Shore N, Van Poppel H, Rathkopf DE, Smith MR, de Bono JS, Logothetis CJ, de Souza P, Fizazi K, Mulders PF, Mainwaring P, Hainsworth JD, Beer TM, North S, Fradet Y, Griffin TA, De Porre P, Londhe A, Kheoh T, Small EJ, Scher HI, Molina A, Ryan CJ. Impact of bone-targeted therapies in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302. Eur Urol. 2015 Oct;68(4):570-7. doi: 10.1016/j.eururo.2015.04.032. Epub 2015 May 16.

    PubMed 25985882

  • Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33. doi: 10.1056/NEJMoa1405095. Epub 2014 Jun 1.

    PubMed 24881730

  • Vanel D, Casadei R, Alberghini M, Razgallah M, Busacca M, Albisinni U. MR imaging of bone metastases and choice of sequence: spin echo, in-phase gradient echo, diffusion, and contrast medium. Semin Musculoskelet Radiol. 2009 Jun;13(2):97-103. doi: 10.1055/s-0029-1220880. Epub 2009 May 19.

    PubMed 19455472

  • Ma J. Dixon techniques for water and fat imaging. J Magn Reson Imaging. 2008 Sep;28(3):543-58. doi: 10.1002/jmri.21492.

    PubMed 18777528

  • Mosavi F, Johansson S, Sandberg DT, Turesson I, Sorensen J, Ahlstrom H. Whole-body diffusion-weighted MRI compared with (18)F-NaF PET/CT for detection of bone metastases in patients with high-risk prostate carcinoma. AJR Am J Roentgenol. 2012 Nov;199(5):1114-20. doi: 10.2214/AJR.11.8351.

    PubMed 23096187

  • Padhani AR, Makris A, Gall P, Collins DJ, Tunariu N, de Bono JS. Therapy monitoring of skeletal metastases with whole-body diffusion MRI. J Magn Reson Imaging. 2014 May;39(5):1049-78. doi: 10.1002/jmri.24548. Epub 2014 Feb 10.

    PubMed 24510426

  • Huang W, Li X, Chen Y, Li X, Chang MC, Oborski MJ, Malyarenko DI, Muzi M, Jajamovich GH, Fedorov A, Tudorica A, Gupta SN, Laymon CM, Marro KI, Dyvorne HA, Miller JV, Barbodiak DP, Chenevert TL, Yankeelov TE, Mountz JM, Kinahan PE, Kikinis R, Taouli B, Fennessy F, Kalpathy-Cramer J. Variations of dynamic contrast-enhanced magnetic resonance imaging in evaluation of breast cancer therapy response: a multicenter data analysis challenge. Transl Oncol. 2014 Feb 1;7(1):153-66. doi: 10.1593/tlo.13838. eCollection 2014 Feb.

    PubMed 24772219

  • Malyarenko DI, Zimmermann EM, Adler J, Swanson SD. Magnetization transfer in lamellar liquid crystals. Magn Reson Med. 2014 Nov;72(5):1427-34. doi: 10.1002/mrm.25034. Epub 2013 Nov 20.

    PubMed 24258798

  • Tombal B, Borre M, Rathenborg P, Werbrouck P, Van Poppel H, Heidenreich A, Iversen P, Braeckman J, Heracek J, Baskin-Bey E, Ouatas T, Perabo F, Phung D, Baron B, Hirmand M, Smith MR. Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naive Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Eur Urol. 2015 Nov;68(5):787-94. doi: 10.1016/j.eururo.2015.01.027. Epub 2015 Feb 14.

    PubMed 25687533

  • Caramella I, Dalla Volta A, Valcamonico F, Bergamini M, Buffoni M, Zivi A, Procopio G, Sepe P, Di Meo N, Foti S, Zamboni S, Messina C, Rizzi A, Lucchini E, Ravanelli M, Zamparini M, Zacchi F, Lagana M, Cosentini D, Bresciani R, Suardi N, Farina D, Berruti A. Multiparametric assessment of bone health in metastatic hormone-sensitive prostate cancer patients receiving androgen deprivation + enzalutamide +/- zoledronic acid (BonEnza study). Bone. 2026 Aug;209:117906. doi: 10.1016/j.bone.2026.117906. Epub 2026 Apr 24.

    PubMed 42035902

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zoledronic Acid and Enzalutamide in people with Prostate Cancer and Bone Metastases, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.

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 8 inclusion and 22 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 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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?

Evaluation of change in bone response after 6 and 12 months of treatment compared to baseline (time frame: Exam will be performed at baseline and after 6 and 12 months of treatment). 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 NCT03336983, which also lists 14 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 1 Aug 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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