An international study to evaluate the safety and effectiveness of enzalutamide plus leuprolide, enzalutamide alone, and leuprolide alone in men with high-risk nonmetastatic prostate cancer progressing after definitive therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medivation Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Aug 2015 → ongoing

Decision date (initial)

2024-07-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medivation, Inc., a wholly owned subsidiary of Pfizer Inc.

External identifiers

EU CT number

2024-513521-23-00

EudraCT number

2014-001634-28

ClinicalTrials.gov

NCT02319837

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

All efficacy objectives will compare enzalutamide plus leuprolide and enzalutamide monotherapy versus placebo plus leuprolide.

Secondary objectives 1

1. All safety objectives will compare enzalutamide plus leuprolide and enzalutamide monotherapy versus placebo plus leuprolide.

Conditions and MedDRA coding

Prostate Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Age 18 years or older and willing and able to provide informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features.
3. Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent. Prostate cryoablation is not considered definitive therapy for this study, but its prior use is not exclusionary.
4. PSA doubling time ≤9 months as calculated by the sponsor.
5. Screening PSA by the central laboratory ≥1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer.
6. Serum testosterone ≥150 ng/dL (5.2 nmol/L) at screening.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
8. Estimated life expectancy of ≥12 months.
9. Able to swallow the study drug and comply with study requirements.
10. Throughout study, the patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) from screening through 3 months after the last dose of study drug or per local guidelines where these require additional description of contraceptive methods. Two acceptable methods of birth control thus include the following: ● Condom (barrier method is required) AND ● One of the following is required: – Established and ongoing use of oral, injected, or implanted hormonal method of contraception by the female partner – Placement of an intrauterine device or intrauterine system by the female partner – Additional barrier method including contraceptive sponge and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner – Tubal ligation in the female partner performed at least 6 months before screening – Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), performed at least 6 months before screening
11. Throughout the study, the patient must use a condom if having sex with a pregnant woman.
12. Must agree not to donate sperm from first dose of study drug through 3 months after the last dose of study drug.

Exclusion criteria 22

1. Prior or present evidence of distant metastatic disease as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) or chest x-ray for soft tissue disease and whole-body radionuclide bone scan for bone disease. Patients with soft tissue pelvic disease may be eligible if the short axis of the largest lymph node is < 20 mm for lymph nodes below aortic bifurcation. If the screening bone scan shows a lesion suggestive of metastatic disease, the patient will be eligible only if a second imaging modality (plain film, CT, MRI) does not show bone metastasis. If the imaging results are equivocal or consistent with metastasis by central radiology review, the patient is not eligible for enrollment. Positron-emission tomography (PET) is not an evaluable imaging modality for this study.
2. Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer ≤36 months in duration and ≥9 months before randomization, or a single dose or a short course (≤6 months) of hormonal therapy given for rising PSA ≥9 months before randomization is allowed.
3. Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer.
4. Prior systemic biologic therapy, including immunotherapy, for prostate cancer.
5. Major surgery within 4 weeks before randomization date.
6. Treatment with 5-alfa reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization.
7. For patients who had a prior prostatectomy, a suitable candidate for salvage radiotherapy as determined by the investigator in consideration of appropriate guidelines (eg, American Society for Radiation Oncology/American Urological Association [ASTRO/AUA]; European Association of Urology [EAU]).
8. Participation in a clinical study of an investigational agent that inhibits the androgen receptor or androgen synthesis (eg, TAK-700, ARN-509, ODM-201); patients who received placebo are allowed.
9. Use of any other investigational agent within 4 weeks before randomization date.
10. Known or suspected brain metastasis or active leptomeningeal disease.
11. History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence. The medical monitor and investigator must agree that the possibility of recurrence is remote.
12. Absolute neutrophil count <1500/µL, platelet count <100,000/µL, or hemoglobin <10 g/dL (6.2 mmol/L) at screening. NOTE: May not have received any growth factors or blood transfusions within 7 days before the hematology values obtained at screening.
13. Total bilirubin (TBili) ≥1.5-times the upper limit of normal (except patients with documented Gilbert’s disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5-times the upper limit of normal at screening.
14. Creatinine >2 mg/dL (177 µmol/L) at screening.
15. Albumin <3.0 g/dL (30 g/L) at screening.
16. History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma). History of loss of consciousness (unless of cardiac origin) or transient ischemic attack within 12 months before randomization.
17. Clinically significant cardiovascular disease including the following: -Myocardial infarction within 6 months before screening; -Unstable angina within 3 months before screening; -New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure unless a screening echocardiogram or multigated acquisition scan performed within 3 months before the randomization date demonstrates a left ventricular ejection fraction ≥45%; -History of clinically significant ventricular arrhythmias (eg, sustained 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 mm Hg at screening; -Bradycardia as indicated by a heart rate of ≤45 beats per minute on the screening electrocardiogram (ECG); -Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure >170 mm Hg or diastolic blood pressure >105 mm Hg at screening.
18. Gastrointestinal disorder affecting absorption.
19. Hypersensitivity reaction to enzalutamide or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
20. Contraindication to the use of leuprolide, such as a previous hypersensitivity reaction to an LHRH analogue or any of the excipients in the leuprolide injection.
21. Ongoing drug or alcohol abuse as per investigator judgment.
22. Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the study, which places the patient at undue risk, or complicates the interpretation of data, in the opinion of the investigator or medical monitor.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate efficacy of the combination of enzalutamide plus leuprolide versus placebo plus leuprolide, as measured by MFS.

Secondary endpoints 2

1. Time to PSA progression: Time to first use of new antineoplastic therapy; Overall survival.
2. To evaluate efficacy, as measured by MFS between enzalutamide monotherapy versus placebo plus leuprolide.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medivation Inc.

Sponsor organisation

Medivation Inc.

Address

525 Market Street Floor 36

City

San Francisco

Postcode

94105-2708

Country

United States

Scientific contact point

Organisation

Medivation Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Medivation Inc.

Contact name

Clinical Medical Lead

Third parties 2

Locations

10 EU/EEA countries · 62 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 53 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications