Phase 3 Study of Pembrolizumab plus Enzalutamide in mCRPC
- Conditions
- Metastatic Castration-Resistant Prostate CancerMedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004117-40-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 1200
A participant will be eligible for inclusion in the study if the participant:
1. Have histologically- or cytologically-confirmed (if acceptable according to local health authority regulations) adenocarcinoma of the prostate without small cell histology. Diagnosis must be stated in a pathology report and confirmed by the investigator.
2. Have prostate cancer progression while on ADT (or post bilateral orchiectomy) within 6 months prior to randomization, as determined by the
investigator, by means of one of the following:
a. PSA progression using local laboratory values as defined by a minimum of 2 consecutive rising PSA levels with an interval of >=1 week
between each assessment where the PSA value at screening should be >=1 ng/mL.
b. Radiographic disease progression in soft tissue based on RECIST 1.1 criteria with or without PSA progression.
c. Radiographic disease progression in bone based on PCWG defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.
3. Have progression under the following conditions if the participant received anti-androgen therapy prior to enrollment:
a. Evidence of progression >4 weeks since last flutamide treatment.
b. Evidence of progression >6 weeks since last bicalutamide or nilutamide treatment.
4. Have current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by CT/MRI.
Participants whose disease spread is limited to regional pelvic lymph nodes are not eligible.
5. Have met one of the following criteria with regards to abiraterone acetate exposure:
a. not received prior abiraterone acetate (ie, abiraterone naïve)
b. received prior abiraterone acetate for the treatment of mHSPC, for a minimum of 4 weeks and must not have progressed while on treatment.
c. received prior abiraterone acetate for the treatment of mCRPC and either progressed on treatment after a minimum of 8 weeks treatment
(minimum 14 weeks for those with bone progression) or become intolerant of the drug after a minimum of 4 weeks treatment.
6. Have ongoing androgen deprivation with serum testosterone <50 ng/mL (<2.0 nM). If the participant is currently being treated with luteinizing hormone-releasing hormone agonists or antagonists (participants who have not undergone an orchiectomy) this therapy must have been initiated at least 4 weeks prior to randomization and treatment must be continued throughout the study.
7. Participants receiving bone resorptive therapy must have been on stable doses for >=4 weeks prior to randomization.
8. Demonstrate adequate organ function as defined in Protocol; all screening labs should be performed in central laboratory within 10 days
of the first dose of study intervention.
9. Participant is male.
10. Participant is >=18 years of age on day of signing the informed consent.
Refer to protocol for the rest of inclucion criteria.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 900
The participant must be excluded from the study if the participant:
1. Has a known additional malignancy that is progressing or has required active treatment in the last 3 years. Participants with basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not
excluded.
2. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents,
corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
4. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study,
interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in
the opinion of the treating investigator.
5. Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and
not recovered adequately from the toxicities and/or complications.
6. Has a gastrointestinal disorder affecting absorption (eg, gastrectomy, active peptic ulcer disease within last 3 months).
7. Is unable to swallow tablets/capsules.
8. Has an active infection (including tuberculosis) requiring systemic therapy.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
10. Has known active human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus (HCV) (eg, HCV RNA. Testing is not required unless mandated by local regulation.
11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain
metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to randomization
and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to randomization. This exception does not include carcinomatous meningitis, which is excluded regardless of
clinical stability.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
13. Has a history of seizure or any condition that may predispose to seizure.
14. Has a history of loss of consciousness within 12 months of the Screening Visit.
15. Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization.
16. Has a history of clinically significant ventricular arrhythmias.
17. Has a history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place.
18. Has hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mmHg) at the Screening Visit.
19. Has bradycardia as indicated by a heart rate of <50 beats per minute on the Screening electrocardiogram (ECG).
Refer to protocol for the rest of exclusion criteria.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method