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

Prostate Carcinoma Clinical Trial

— ENZART  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03196388
• Other study ID #: 2015-004617-25
• Status: Recruiting
• Phase: Phase 2
• First received: June 20, 2017
• Last updated: January 17, 2018
• Start date: December 27, 2017
• Est. completion date: December 2018

Study information

• Verified date: January 2018
• Source: Fundación Canaria de Investigación Sanitaria
• Contact: Pedro Carlos Lara Jiménez, MD, PhD
• Phone: 00 34 928450284
• Email: pedrocarlos.lara[@]ulpgc.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

The participant will be given a study drug-dosing diary for each of 6 treatment cycles. Each treatment cycle lasts 28 days (4 weeks), during which time the participant will be taking the study drug enzalutamide by mouth (4 pills daily). The diary will also include special instructions for taking the enzalutamide.

The participant will also be undergoing external beam radiation therapy during the study, for a duration of 5,5 weeks. Treatment will be administered on an outpatient basis. This part of the study is considered standard of care.

The participant will be required to have IGRT either by ConeBeam CT study and/or fiducial markers placed within the prostate as part of this study. These are very small gold markers that are placed in the prostate. This procedure is similar to the biopsy that the participant had to diagnose their cancer. These both procedures are routinely performed to permit imaging and position corrections to improve the precision of the external beam (radiation) delivery (Image Guided Radiation Therapy). This is also considered standard of care and is not experimental.

Planned Follow-up: Participants will be followed on study at a 3 month follow-up after treatment (cessation of enzalutamide). Additional follow-up to assess the status of the participant's cancer will be conducted at the discretion of the treating physicians as part of the participant's routine medical care.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: December 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 95 Years

Eligibility

Inclusion Criteria:

• 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:

1. Leukocytes =3,000/mcL

2. Platelets =80,000/mcL

3. Total bilirubin < 2X institutional upper limit

4. AST (SGOT)/ALT (SGPT) = 2.5 X institutional upper limit of normal

5. 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

Exclusion Criteria:

• 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:

1. Myocardial infarction within 6 months of enrollment

2. Uncontrolled angina within 3 months of enrollment

3. 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%;

4. History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);

5. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;

6. Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive measurements at the Screening visit;

7. Bradycardia as indicated by a heart rate < 50 beats per minute at the Screening visit;

8. Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the screening visit;

9. EKG demonstrating equal to or greater than grade III toxicity according the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of oral study drug(s) within 3 months of enrollment.

• Major surgery within 4 weeks of registration.

• Previous use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988); ketoconazole.

• Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, places the patient at undue risk, or complicates the interpretation of safety data.

• Use of herbal or alternative remedies that may affect hormonal status such as Prostasol or PC-SPES.

Related Conditions & MeSH terms

• Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
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

Locations

Country	Name	City	State
Spain	Hospital Ramón y Cajal	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Canaria de Investigación Sanitaria	Hospital Universitario de Canarias

Country where clinical trial is conducted

Spain, 

References & Publications (11)

Belikov S, Öberg C, Jääskeläinen T, Rahkama V, Palvimo JJ, Wrange Ö. 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.m — View Citation

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. — View Citation

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 rand — View Citation

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 200 — View Citation

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 — View Citation

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, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survi — View Citation

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. Review. — View Citation

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-naï — View Citation

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 o — View Citation

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 — View Citation

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 prosta — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with more or equal 80% reduction of baseline PSA		25 week after treatment

External Links

•   BICALUTAMIDE MONOTHERAPY COMPARED WITH CASTRATION IN PATIENTS WITH NONMETASTATIC LOCALLY ADVANCED PROSTATE CANCER: 6.3 YEARS OF FOLLOWUP
•   Cross-sectional study of bone turnover during bicalutamide monotherapy for prostate cancer
•   Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): ResuEnzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study.lts of phase III PREVAIL study.