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

NCT03336983 | Completed Phase 2 DMC

• 2 other identifiers: ASCB-ONCO-2336-20172017-000305-21
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer; Bone Metastases

Keywords

prostate cancer; bone metastasis; enzalutamide; zoledronic acid

Outcome Measures

Primary Outcomes (1)

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

  Whole-body Diffusion MRI

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

Secondary Outcomes (7)

• Evaluation of bone repair

  Screening visit; 12 months of treatment

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

  Screening visit; 18 months of treatment

• Functional Assessment of Cancer Therapy-Prostate

  Monthly until end of treatment (18 months)

• Brief Pain Inventory-Short Form Questionnaire

  Monthly until end of treatment (18 months)

• Weight evaluation

  Screening visit; 18 months of treatment

Study Arms (2)

LHRH-A + Enzalutamide

OTHER

Prostate cancer patients with hormone sensitive metastatic bone disease will be treated with LHRH-A + Enzalutamide until patient's progression, consent withdrawal or unacceptable toxicity

Drug: Enzalutamide

LHRH-A + Enzalutamide + Zoledronic Acid

EXPERIMENTAL

Prostate 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

Drug: Zoledronic Acid; Drug: Enzalutamide

Interventions

Zoledronic Acid DRUG

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

Also known as: Zoledronate

LHRH-A + Enzalutamide + Zoledronic Acid

Enzalutamide DRUG

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

Also known as: Xtandi

LHRH-A + Enzalutamide; LHRH-A + Enzalutamide + Zoledronic Acid

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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;

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Related Publications (13)

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• 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.

  PMID: 22826385 BACKGROUND

• 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.

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• 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.

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• 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.

  PMID: 25985882 RESULT

• 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.

  PMID: 24881730 RESULT

• 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.

  PMID: 19455472 RESULT

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

  PMID: 18777528 RESULT

• 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.

  PMID: 23096187 RESULT

• 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.

  PMID: 24510426 RESULT

• 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.

  PMID: 24772219 RESULT

• 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.

  PMID: 24258798 RESULT

• 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.

  PMID: 25687533 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Zoledronic Acid; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Alfredo Berruti, MD

  ASST Spedali Civili di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: prostate cancer patients with hormone sensitive metastatic bone disease

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: November 8, 2017
• Study Start: December 1, 2017
• Primary Completion: June 30, 2022
• Study Completion: April 1, 2023
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)