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JOURNAL ONKOLOGIE – STUDIE

Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921)

Rekrutierend

NCT-Nummer:
NCT03834506

Studienbeginn:
Mai 2019

Letztes Update:
07.05.2021

Wirkstoff:
Pembrolizumab, Docetaxel, Prednisone, Placebo, Dexamethasone

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Männer

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 214)

Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)
79106 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +4976127028930
» Ansprechpartner anzeigen
Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)
90419 Nuernberg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49911398114729
» Ansprechpartner anzeigen
University of Southern California Norris Comprehensive Cancer Center ( Site 0061)
90033 Los Angeles
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 323-865-3000
» Ansprechpartner anzeigen
University of California San Francisco ( Site 0023)
94158 San Francisco
United StatesAktiv, nicht rekrutierend» Google-Maps
Methodist Hospital- Merriillville ( Site 0008)
46410 Merrillville
United StatesAbgeschlossen» Google-Maps
Karmanos Cancer Institute ( Site 0077)
48201 Detroit
United StatesAbgeschlossen» Google-Maps
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)
07601 Hackensack
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 551-996-5900
» Ansprechpartner anzeigen
Associated Medical Professionals of NY ( Site 0060)
13210 Syracuse
United StatesAbgeschlossen» Google-Maps
Virginia Cancer Institute ( Site 0052)
23230 Richmond
United StatesAbgeschlossen» Google-Maps
Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)
C1012AAR Buenos Aires
ArgentinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +5491130051657
» Ansprechpartner anzeigen
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)
90610-000 Porto Alegre
BrazilRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +555133203039
» Ansprechpartner anzeigen
The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 1309)
310009 Hangzhou
ChinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +86057187783759
» Ansprechpartner anzeigen
Hospital Pablo Tobon Uribe ( Site 1066)
050034 Medellin
ColombiaAbgeschlossen» Google-Maps
Biomelab S A S ( Site 1067)
080002 Barranquilla
ColombiaAbgeschlossen» Google-Maps
Assaf Harofeh MC ( Site 0547)
7030001 Beer Yaakov-Zerifin
IsraelAbgeschlossen» Google-Maps
Nara Medical University Hospital ( Site 0715)
634-8522 Kashihara
JapanAktiv, nicht rekrutierend» Google-Maps
Samsung Medical Center ( Site 0172)
06351 Seoul
Korea, Republic ofAbgeschlossen» Google-Maps
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)
454087 Chelyabinsk
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)
660133 Krasnoyarsk
Russian FederationAktiv, nicht rekrutierend» Google-Maps
SBIH City clinical hospital named after D.D. Pletniov ( Site 0575)
105077 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Russian Scientific Center of Radiology ( Site 0559)
117485 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
National Medical Research Radiological Center ( Site 0556)
125284 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Volga District Medical Center Federal Medical and Biological Agency ( Site 0572)
603074 Nizhny Novgorod
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +78314216969
» Ansprechpartner anzeigen
Omsk Clinical Oncology Dispensary ( Site 0568)
644013 Omsk
Russian FederationAktiv, nicht rekrutierend» Google-Maps
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)
443031 Samara
Russian FederationAbgeschlossen» Google-Maps
Clinical Research Center of specialized types medical care-Oncology ( Site 0570)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79219697585
» Ansprechpartner anzeigen
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)
197758 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
SPb SBHI City Clinical Oncological Dispensary ( Site 0571)
198255 Saint Petersburg
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Leningrad Regional Oncology Center ( Site 0588)
188663 Saint-Petersburg
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Tomsk National Research Medical Center of Russian Academy of Sciences ( Site 0579)
634050 Tomsk
Russian FederationAbgeschlossen» Google-Maps
National Cheng Kung University Hospital ( Site 0134)
704 Tainen
TaiwanAbgeschlossen» Google-Maps
National Taiwan University Hospital ( Site 0131)
10048 Taipei
TaiwanAktiv, nicht rekrutierend» Google-Maps
Taipei Veterans General Hospital ( Site 0135)
11217 Taipei
TaiwanAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to assess the efficacy and safety of the combination of

pembrolizumab (MK-3475) and docetaxel in the treatment of men with metastatic

castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC but

have progressed on or are intolerant to Next Generation Hormonal Agent (NHA).

There are two primary study hypotheses.

Hypothesis 1: The combination of pembrolizumab plus docetaxel plus prednisone is superior to

placebo plus docetaxel plus prednisone with respect to Overall Survival (OS).

Hypothesis 2: The combination of pembrolizumab plus docetaxel plus prednisone is superior to

placebo plus docetaxel plus prednisone with respect to Radiographic Progression-free Survival

(rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in

Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without

small cell histology

- Has prostate cancer progression while on androgen deprivation therapy (or post

bilateral orchiectomy) within 6 months prior to screening

- Has current evidence of metastatic disease documented by either bone lesions on bone

scan and/or soft tissue disease by computed tomography/magnetic resonance imaging

(CT/MRI)

- Has received prior treatment with one (but not more than one) NHA (eg, abiraterone

acetate, enzalutamide, apalutamide, or darolutamide) for metastatic hormone-sensitive

prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC) and either a)

progressed through treatment OR b) has become intolerant of the drug

- Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)

- Participants receiving bone resorptive therapy (including, but not limited to,

bisphosphonate or denosumab) must have been on stable doses prior to randomization

- Participants must agree to the following during the study treatment period and for at

least 120 days after the last dose of pembrolizumab or for at least 180 days after the

last dose of docetaxel (whichever is longer): Refrain from donating sperm PLUS Use

contraception unless confirmed to be azoospermic (vasectomized or secondary to medical

cause)

- Participants must agree to use male condom when engaging in any activity that allows

for passage of ejaculate to another person of any sex

- Has provided newly obtained core or excisional biopsy (obtained within 12 months of

screening) from soft tissue not previously irradiated (samples from tumors progressing

in a prior site of radiation are allowed). Participants with bone only or bone

predominant disease may provide a bone biopsy sample

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed

within 7 days of randomization

Exclusion Criteria:

- Has a known additional malignancy that is progressing or has required active treatment

in the last 3 years

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

- 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

- Has a gastrointestinal disorder affecting absorption or is unable to swallow

tablets/capsules

- Has an active infection (including tuberculosis) requiring systemic therapy

- Has a history of (non-infectious) pneumonitis that required steroids or current

pneumonitis

- Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or

hepatitis C virus (HCV) infection

- Has known active central nervous system (CNS) metastases and/or carcinomatous

meningitis

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients

- Has symptomatic congestive heart failure (New York Heart Association Class III or IV

heart disease)

- Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization or who

has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to mAbs

- Has used herbal products that may have hormonal anti-prostate cancer activity and/or

are known to decrease PSA levels (e.g. saw palmetto) prior to randomization

- Has received prior treatment with radium or other therapeutic radiopharmaceuticals for

prostate cancer

- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),

anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent

directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic

T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)

- Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC

- Has hypersensitivity to docetaxel or polysorbate 80

- Is currently receiving either strong or moderate inhibitors of cytochrome P450

(CYP)3A4 that cannot be discontinued for the duration of the study

- Has received prior targeted small molecule therapy or abiraterone acetate,

enzalutamide, apalutamide, or darolutamide within 4 weeks prior to the first dose of

study treatment, or has not recovered (i.e., Grade ≤1 or at baseline) from AEs due to

a previously administered agent

- Has received prior radiotherapy to within 2 weeks of start of study treatment.

Participants must have recovered from all radiation-related toxicities, not require

corticosteroids, and not have had radiation pneumonitis

- Has received a live vaccine within 30 days prior to randomization

- Has received treatment with 5α reductase inhibitors (eg, finasteride or dutasteride),

estrogens, and/or cyproterone within 4 weeks prior to randomization

- Has received prior treatment with ketoconazole for prostate cancer

- Is currently participating in or has participated in a study of an investigational

agent or has used an investigational device within 4 weeks prior to the first dose of

study treatment

- Has a "superscan" bone scan

- Is expecting to conceive or father children within the projected duration of the

study, starting with the screening visit through 120 days after the last dose of study

treatment

- Has had an allogenic tissue/solid organ transplant

Studien-Rationale

Primary outcome:

1. Overall Survival (OS) (Time Frame - Up to approximately 28 months):
Time from randomization to death due to any cause

2. Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (Time Frame - Up to approximately 28 months):
Time from randomization to radiographic progression, or death due to any cause, whichever occurs first

Secondary outcome:

1. Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST) (Time Frame - Up to approximately 28 months):
Time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurs first

2. Prostate-specific Antigen (PSA) Response Rate (Time Frame - Up to approximately 28 months):
Percentage of participants in the analysis population who have a negative change (decrease) in PSA level of ≥50% measured twice ≥3 weeks apart

3. Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (Time Frame - Up to approximately 28 months):
Percentage of participants in the analysis population who have a best overall response of either confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1

4. Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (Time Frame - Up to approximately 28 months):
Time from first documented evidence of confirmed Complete Response (CR) or Partial Response (PR) per PCWG-modified RECIST 1.1 until disease progression or death from any cause, whichever occurs first

5. Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score) (Time Frame - Up to approximately 28 months):
Time from randomization to pain progression. In this study, pain progression will be assessed by participant responses to Item 3 of the BPI-SF and participant AQA Scores which are both assessed by participants daily for 7 consecutive days

6. Time to First Symptomatic Skeletal-related Event (SSRE) (Time Frame - Up to approximately 28 months):
Time from randomization to the first SSRE. SSRE is defined as radiation to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathological fracture, spinal cord compression, or surgery to bone

7. Time to Prostate-specific Antigen (PSA) Progression (Time Frame - Up to approximately 28 months):
Time from randomization to PSA progression. PSA progression date is defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline

8. Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (Time Frame - Up to approximately 28 months):
Time from randomization to radiographic soft tissue progression per PCWG-modified RECIST 1.1

9. Number of Participants Who Experience an Adverse Event (AE) (Time Frame - Up to approximately 28 months):
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment

10. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) (Time Frame - Up to approximately 28 months):
The number of participants who discontinue study treatment due to an AE will be presented

Studien-Arme

  • Experimental: Pembrolizumab+Docetaxel
    On Day 1 of each 21-day cycle, participants receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours and 1 hour prior to docetaxel administration PLUS docetaxel 75 mg/m^2 by intravenous (IV) infusion for up to a maximum of 10 cycles (approximately 7 months). Participants receive prednisone 5 mg by oral tablets twice daily during each docetaxel cycle up to a maximum of 10 cycles (approximately 7 months). Participants also receive pembrolizumab 200 mg by IV infusion on day 1 of each 21-day cycle for up to a maximum of 35 cycles (approximately 2 years).
  • Placebo Comparator: Placebo+Docetaxel
    On Day 1 of each 21-day cycle, participants receive dexamethasone 8 mg by oral tablets at 12 hours, 3 hours and 1 hour prior to docetaxel administration PLUS docetaxel 75 mg/m^2 by IV infusion for up to a maximum of 10 cycles (approximately 7 months). Participants receive prednisone 5 mg by oral tablets twice daily during each docetaxel cycle up to a maximum of 10 cycles (approximately 7 months). Participants also receive placebo by IV infusion on day 1 of each 21-day cycle for up to a maximum of 35 cycles (approximately 2 years).

Geprüfte Regime

  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    IV infusion
  • Docetaxel (TAXOTERE®):
    IV infusion
  • Prednisone:
    Oral tablets
  • Placebo (Normal saline or dextrose infusion):
    IV infusion
  • Dexamethasone (DECADRON®):
    Oral tablets

Quelle: ClinicalTrials.gov


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