Enzalutamide and External Beam Hypofractionated Radiotherapy For Intermediate Risk Localized Prostate Cancer

NCT03196388 | Unknown Phase 2 DMC

• 1 other identifier: 2015-004617-25
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is evaluating a drug called enzalutamide in combination with external beam radiation therapy as a possible treatment for prostate cancer. Presently, when participants receive hormonal therapy with radiation therapy for prostate cancer, medications are given to reduce testosterone levels in the blood stream. This leads to side effects such as loss of sex drive, erectile dysfunction (ED) and decrease in muscle strength. The purpose of this study is test another form of hormonal therapy with radiationtherapy. The medication called enzalutamide will be used with radiation therapy. Instead of lowering testosterone, enzalutamide blocks testosterone in cells. This study will test if enzalutamide when used with radiation will lower the PSA without causing the side effects associated with medications that lower testosterone in the blood stream

Conditions

Prostate Carcinoma

Keywords

ENZALUTAMIDE; External Beam Hypofractionated Radiotherapy Intermediate Risk Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients with more or equal 80% reduction of baseline PSA

  25 week after treatment

Study Arms (1)

Enzalutamide with External

EXPERIMENTAL

On this study patients will be treated with 6 months of Xtandi (enzalutamide). Approximately one-third of the way through this treatment they will receive EBRT. Starting on Day 1, all patients will ingestenzalutamide 160 mg/day at the same time each day without breaks (except as outlined for toxicity), with or without food, for 6 (28 day +/-3 days) cycles. Dose reduction of enzalutamide to 120 mg/day is allowed with the approval of the Medical Monitor. Patients will be instructed to return all unused capsules at each study visit to assess compliance and will receive study drug every 28 days (+/-3 days) for 6 cycles (25 weeks).

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Radiation: External Beam Radiation Dose will be normalized such that exactly 98% of the PTV (planned target volume) receives the prescription dose and will be scored as per protocol. The maximum allowable dose within the PTV is 107% of the prescribed dose to a volume that is at least 0.03 cc. The minimum allowable dose within the PTV is \>95% of the prescribed dose to a volume that is at least 0.03 cc. EBRT shall receive prescription doses to the PTV 70 Gy delivered in 2.5 Gy

Also known as: XTANDI

Enzalutamide with External

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Life expectancy of greater than 1 year.
• Diagnosis of histologically confirmed prostate carcinoma
• ECOG Score ≤ 1
• Participants must have an adequate organic function, defined as:
• Leukocytes ≥3,000/mcL
• Platelets ≥80,000/mcL
• Total bilirubin \< 2X institutional upper limit
• AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
• Creatinine \< 2x institutional limits .
• Potentially fertile patients should use effective contraceptive methods (barrier methods plus other contraceptive methods) before entering the study and during their participation in the study
• Ability to understand and the willingness to sign a written informed consent
• Patients should be available for clinical follow-up.
• To be able to swallow the medication of the study and to fulfill the requirements of the same one

You may not qualify if:

• Received an investigational agent within 4 weeks prior to enrollment
• Stage T4 prostate cancer by clinical examination or radiologic evaluation.
• Hypogonadism or severe androgen deficiency as defined by screening serum testosterone less than 50 ng/dL below the normal range for the institution.
• Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer.
• Receiving concurrent androgens, anti-androgens, estrogens, or progestational agents, or received any of these agents within the 6 months prior to enrollment or having taken finasteride or dutasteride within 30 days of registration.
• History of another active malignancy within the previous 5 years other than curatively treated nonmelanomatous skin cancer and superficial bladder cancer. Participants treated for malignancy with no relapse within two years are eligible to participate in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment.
• History of seizure or any condition or concurrent medication that may predispose to seizure.
• History of loss of consciousness or transient ischemic attack within 12 months prior to enrollment.
• Clinically significant cardiovascular disease, including:
• Myocardial infarction within 6 months of enrollment
• Uncontrolled angina within 3 months of enrollment
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction ≥ 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;

Sponsors & Collaborators

• Fundación Canaria de Investigación Sanitaria: lead
• Hospital Universitario de Canarias: collaborator

Study Sites (1)

Hospital Ramón y Cajal

Madrid, Spain

RECRUITING

Related Publications (11)

• Boccon-Gibod L, Tombal B. Open to debate. The motion: Hormonal blockade should be limited due to significant adverse effects. Eur Urol. 2009 Jan;55(1):240-3. doi: 10.1016/j.eururo.2008.10.006. Epub 2008 Oct 14. No abstract available.

  PMID: 18930581 RESULT

• Keating NL, O'Malley AJ, Freedland SJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst. 2010 Jan 6;102(1):39-46. doi: 10.1093/jnci/djp404. Epub 2009 Dec 7.

  PMID: 19996060 RESULT

• Taylor LG, Canfield SE, Du XL. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer. 2009 Jun 1;115(11):2388-99. doi: 10.1002/cncr.24283.

  PMID: 19399748 RESULT

• Tyrrell CJ, Kaisary AV, Iversen P, Anderson JB, Baert L, Tammela T, Chamberlain M, Webster A, Blackledge G. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol. 1998;33(5):447-56. doi: 10.1159/000019634.

  PMID: 9643663 RESULT

• Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009 May 8;324(5928):787-90. doi: 10.1126/science.1168175. Epub 2009 Apr 9.

  PMID: 19359544 RESULT

• Belikov S, Oberg C, Jaaskelainen T, Rahkama V, Palvimo JJ, Wrange O. FoxA1 corrupts the antiandrogenic effect of bicalutamide but only weakly attenuates the effect of MDV3100 (Enzalutamide). Mol Cell Endocrinol. 2013 Jan 5;365(1):95-107. doi: 10.1016/j.mce.2012.10.002. Epub 2012 Oct 11.

  PMID: 23063623 RESULT

• 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.

  PMID: 22894553 RESULT

• Trump D. Commentary on: "Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study." 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, Hirmand M, Smith MR. Institut de Recherche Clinique, Universite Catholique de Louvain, Brussels, Belgium. Electronic address: bertrand.tombal@uclouvain.be. Aarhus University Hospital, Aarhus, Denmark. Herlev Hospital, Herlev, Denmark. AZ Groeninge Kortrijk, Kortrijk, Belgium. UZ Leuven, Leuven, Belgium. Klinik und Poliklinik fur Urologie, RWTH University Aachen, Aachen, Germany. Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. UZ Brussel, Brussels, Belgium. Univerzita Karlova v Praze, Prague, Czech Republic. Astellas Pharma Global Development, Leiden, Netherlands. Astellas Pharma Global Development, Northbrook, IL, USA. Medivation Inc, San Francisco, CA, USA. Massachusetts General Hospital Cancer Center, Boston, MA, USA: Lancet Oncol. 2014 May;15(6):592-600; doi: 10.1016/S1470-2045(14)70129-9. [Epub 2014 Apr 14]. Urol Oncol. 2016 May;34(5):248-9. doi: 10.1016/j.urolonc.2015.03.012. Epub 2015 Apr 30.

  PMID: 25937426 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

• Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D, Forer D, Hirmand M, de Bono JS. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014 Sep;15(10):1147-56. doi: 10.1016/S1470-2045(14)70303-1. Epub 2014 Aug 4.

  PMID: 25104109 RESULT

• Loriot Y, Miller K, Sternberg CN, Fizazi K, De Bono JS, Chowdhury S, Higano CS, Noonberg S, Holmstrom S, Mansbach H, Perabo FG, Phung D, Ivanescu C, Skaltsa K, Beer TM, Tombal B. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 2015 May;16(5):509-21. doi: 10.1016/S1470-2045(15)70113-0. Epub 2015 Apr 14.

  PMID: 25888263 RESULT

Related Links

• Cross-sectional study of bone turnover during bicalutamide monotherapy for prostate cancer

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

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

Study Officials

• Pedro Carlos Lara Jiménez, MD, PhD

  Hospital Universitario de Gran Canaria Dr. Negrín

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pedro Carlos Lara Jiménez, MD, PhD

CONTACT

00 34 928450284; pedrocarlos.lara@ulpgc.es

Vanessa Pacual Alfaro

CONTACT

00 34 928450259; vanepasal@hotmail.com

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: June 20, 2017
• First Posted: June 22, 2017
• Study Start: December 27, 2017
• Primary Completion: June 1, 2018
• Study Completion: December 1, 2018
• Last Updated: January 18, 2018

Record last verified: 2018-01

Locations

ES (1)