A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients With Visceral Disease.

Carcinoma Prostate Clinical Trial

— EXCALIBUR  

Official title:

A Phase II Study Evaluating the Efficacy of Enzalutamide and the Role of ARv7 in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients With Visceral Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03103724
• Other study ID #: INT 178-15
• Status: Completed
• Phase: Phase 2
• Start date: March 16, 2017
• Est. completion date: April 23, 2021

Study information

• Verified date: April 2021
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open label, single arm, phase II multicentre study designed to determine the clinical benefit, as measured by 3-months disease control rate (DCR) provided by enzalutamide in metastatic Castration Resistant Prostate Cancer patients with at least one visceral site involvement.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: April 23, 2021
• Est. primary completion date: April 23, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age > 18

2. ECOG PS 0-1-2

3. Biopsy (primary tumour or metastases) confirming the diagnosis of prostate adenocarcinoma

4. Documented measurable metastatic visceral disease (according to RECIST 1.1 criteria) considering metastases in lung or liver or extraregional lymphnodes

5. Written informed consent

6. Platelets > or = 100 x109/L; haemoglobin > or = 9 g/dl; neutrophils > or 1.5 x 109/L

7. Bilirubin < or = 2 mg/dl, AST and ALT < or = 2.5 times the UNL or < or = 5 times UNL for pts with liver metastases; serum albumin > or = the LNL

8. Patients of childbearing age should use contraceptive methods

9. Life expectancy > 3 months

10. Able to swallow the study drug and comply with study requirements;

11. Willing and able to give informed consent.

12. Ongoing androgen deprivation therapy with a GnRH analogue or orchiectomy (i.e., surgical or medical castration);

13. Patients may have received previous therapy including chemotherapy (docetaxel) last cycle must be received 3 weeks before start of experimental treatment. Hormonal treatment containing bicalutamide must be interrupted 2 weeks before start of study therapy

14. Previous radiotherapy (prostate and/or bone) is accepted but must be interrupted 3 weeks before start of experimental treatment.

15. Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit

16. Progressive disease by PSA or imaging in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the

following three criteria (according with PCWG2):

• PSA progression defined by a minimum of three rising PSA levels with an interval of = 1 week between each determination. The PSA value at the Screening visit should be = 2 g/L (2 ng/ml); if the third PSA value is less than second PSA, a fourth PSA must be repeated and if it the value is higher than second must be considered as disease
• Soft tissue/visceral disease progression defined by RECIST 1.1;
• Bone disease progression defined by two or more new lesions on bone scan.

Exclusion Criteria:

1. Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment;

2. Metastases in the brain or active epidural disease;

3. History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer;

4. History of seizure, including any febrile seizure, loss of consciousness, or transient ischemia attack within 12 months of enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, head trauma with loss of consciousness requiring hospitalization);

5. Clinically significant cardiovascular disease including: Myocardial infarction within 6 months; Uncontrolled angina within 3 months; Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is = 45%;

6. Diagnosed or suspected congenital long QT syndrome;

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

8. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer within last 3 months);

9. Major surgery within 4 weeks prior to enrollment (Day 1 visit);

10. Prior treatment with abiraterone acetate;

11. Participation in a clinical trial about an experimental anti-androgen agent (eg. ARN-509, ODM-201, VT-464, except for placebo arm);

12. Treatment (concomitant or in the previous 2 weeks) with anti-androgens (eg. Bicalutamide, nilutamide, flutamide) or 5-a reductase inhibitors (eg. finasteride, dutasteride).

Related Conditions & MeSH terms

• Carcinoma Prostate
• Prostatic Neoplasms

Intervention

Drug:
• Xtandi
Enzalutamide 160 mg (4 x 40 mg capsules), orally once daily

Locations

Country	Name	City	State
Italy	Elena Verzoni	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

References & Publications (18)

Ahmed M, Li LC. Adaptation and clonal selection models of castration-resistant prostate cancer: current perspective. Int J Urol. 2013 Apr;20(4):362-71. doi: 10.1111/iju.12005. Epub 2012 Nov 19. Review. — View Citation

Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, Chen Y, Mohammad TA, Chen Y, Fedor HL, Lotan TL, Zheng Q, De Marzo AM, Isaacs JT, Isaacs WB, Nadal R, Paller CJ, Denmeade SR, Carducci MA, Eisenberger MA, Luo J. AR-V7 and resistance to enzalut — View Citation

Arlen PM, Bianco F, Dahut WL, D'Amico A, Figg WD, Freedland SJ, Gulley JL, Kantoff PW, Kattan MW, Lee A, Regan MM, Sartor O; Prostate Specific Antigen Working Group. Prostate Specific Antigen Working Group guidelines on prostate specific antigen doubling — View Citation

Astellas Pharma Ltd. Xtandi (enzalutamide) 40mg soft capsules. Summary of Product Characteristics. 26 June 2013.

Beer TM, Tombal B. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Oct 30;371(18):1755-6. doi: 10.1056/NEJMc1410239. — View Citation

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (v — View Citation

Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010 Mar;46(4):765-81. doi: 10.1016/j.ejca.2009.12.014. Epub 2010 Jan 29. — View Citation

Fitzpatrick JM, de Wit R. Taxane mechanisms of action: potential implications for treatment sequencing in metastatic castration-resistant prostate cancer. Eur Urol. 2014 Jun;65(6):1198-204. doi: 10.1016/j.eururo.2013.07.022. Epub 2013 Jul 25. Review. — View Citation

Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N; European Association of Urology. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-res — View Citation

Horwich A, Parker C, de Reijke T, Kataja V; ESMO Guidelines Working Group. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013 Oct;24 Suppl 6:vi106-14. doi: 10.1093/annonc/mdt208. Epub 2013 Jun 27. — View Citation

Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Feb;167(2 Pt 2):948-51; discussion 952. — View Citation

Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression--implications for drug resistance. Nat Rev Clin Oncol. 2013 Oct;10(10):571-87. doi: 10.1038/nrclinonc.2013.158. Epub 2013 Sep 3. Review. — View Citation

Merseburger AS, Bellmunt J, Jenkins C, Parker C, Fitzpatrick JM; European Treatment Practices Group. Perspectives on treatment of metastatic castration-resistant prostate cancer. Oncologist. 2013;18(5):558-67. doi: 10.1634/theoncologist.2012-0478. Epub 20 — View Citation

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. — View Citation

Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, — View Citation

Ryan CJ, Tindall DJ. Androgen receptor rediscovered: the new biology and targeting the androgen receptor therapeutically. J Clin Oncol. 2011 Sep 20;29(27):3651-8. doi: 10.1200/JCO.2011.35.2005. Epub 2011 Aug 22. Review. — View Citation

Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate — 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

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Control Rate (DCR)	To determine the clinical benefit, as measured by 3 months disease control rate (DCR) provided by enzalutamide in mCRPC patients with visceral disease.	3 months
Secondary	Safety of the treatment per NCI-CTCA v. 4.0	To determine the safety of the treatment according to NCI-CTCA v. 4.0	2 years
Secondary	Quality of life by EQ-5D-5L e FACT-P	To evaluate quality of life as assessed by EQ-5D-5L e FACT-P questionnaire	2 years
Secondary	Pain assessment	To evaluate pain as assessed by BPI-SF questionnaire	2 years