Dienstag, 21. Mai 2019
Navigation öffnen
Anzeige:

JOURNAL ONKOLOGIE – STUDIE

Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)

Rekrutierend

NCT-Nummer:
NCT03142334

Studienbeginn:
Juni 2017

Letztes Update:
17.05.2019

Wirkstoff:
Placebo (saline solution), Pembrolizumab

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Renal Cell

Geschlecht:
Alle

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 244)

Universitatsklinikum Dusseldorf ( Site 2108)
40225 Dusseldorf
(Nordrhein-Westfalen)
GermanyAbgeschlossen» Google-Maps
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 2111)
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +496131170
» Ansprechpartner anzeigen
Arizona Oncology Associates, PC- HAL ( Site 8018)
85016 Phoenix
United StatesAbgeschlossen» Google-Maps
Illinois Cancer Specialists ( Site 8001)
60714 Niles
United StatesAbgeschlossen» Google-Maps
Quest Research Institute ( Site 0036)
48073 Royal Oak
United StatesAbgeschlossen» Google-Maps
Comprehensive Cancer Centers of Nevada ( Site 8013)
89148 Las Vegas
United StatesAbgeschlossen» Google-Maps
Montefiore Medical Center ( Site 0009)
10461 Bronx
United StatesAbgeschlossen» Google-Maps
Avera Cancer Institute ( Site 0023)
57105 Sioux Falls
United StatesAbgeschlossen» Google-Maps
Texas Oncology-Denton South ( Site 8016)
76210 Denton
United StatesAbgeschlossen» Google-Maps
Texas Oncology- Paris ( Site 8004)
75460-5004 Paris
United StatesAbgeschlossen» Google-Maps
CTRC at The University of Texas Health Science Center at San Antonio ( Site 0026)
78229 San Antonio
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 210-450-5798
» Ansprechpartner anzeigen
Texas Oncology-Waco ( Site 8012)
76712 Waco
United StatesAbgeschlossen» Google-Maps
Medical Oncology Associates (Summit Cancer Centers) ( Site 0005)
99208 Spokane
United StatesAbgeschlossen» Google-Maps
Yakima Valley Memorial Hospital North Star Lodge ( Site 8017)
98902 Yakima
United StatesAbgeschlossen» Google-Maps
University of Wisconsin Carbone Cancer Center ( Site 0019)
53792 Madison
United StatesAbgeschlossen» Google-Maps
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1001)
90610-000 Porto Alegre
BrazilRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +555199892554
» Ansprechpartner anzeigen
Dr. Leon Richard Oncology Centre ( Site 0106)
E1C 8X3 Moncton
CanadaAbgeschlossen» Google-Maps
William Osler Health System ( Site 0115)
L6R 3J7 Brampton
CanadaAbgeschlossen» Google-Maps
Hospital Regional de La Serena ( Site 0907)
1710216 La Serena
ChileAbgeschlossen» Google-Maps
Hospital Regional Rancagua Libertador Bernardo O Higgins ( Site 0910)
2820000 Rancagua
ChileAbgeschlossen» Google-Maps
Hospital Militar de Santiago ( Site 0911)
7850000 Santiago
ChileAbgeschlossen» Google-Maps
Fundacion CardioInfantil Instituto de Cardiologia ( Site 0803)
110131 Bogota
ColombiaAbgeschlossen» Google-Maps
Fakultni nemocnice v Motole ( Site 1504)
150 06 Praha 5
CzechiaAbgeschlossen» Google-Maps
Centre Rene Gauducheau ICO ( Site 2207)
44805 Saint Herblain
FranceAbgeschlossen» Google-Maps
Osaka Rosai Hospital ( Site 0418)
591-8025 Sakai
JapanAktiv, nicht rekrutierend» Google-Maps
Severance Hospital Yonsei University Health System ( Site 0303)
03722 Seoul
Korea, Republic ofAbgeschlossen» Google-Maps
Mazowiecki Szpital Onkologiczny ( Site 1316)
05-135 Wieliszew
PolandAbgeschlossen» Google-Maps
Wojskowy Instytut Medyczny Centralny Szpital Medyczny MON ( Site 1300)
04-141 Warszawa
PolandAbgeschlossen» Google-Maps
Russian Scientific Center of Radiology and Surgical Technologies ( Site 1205)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79219629807
» Ansprechpartner anzeigen
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1217)
450054 Ufa
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79373010101
» Ansprechpartner anzeigen
Hospital Universitario Ramon y Cajal ( Site 1800)
28034 Madrid
SpainAktiv, nicht rekrutierend» Google-Maps
Chang Gung Medical Foundation. Linkou ( Site 0203)
333 Taoyuan
TaiwanAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Participants will be assigned to receive study treatment until disease recurrence, unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the participant, noncompliance with study treatment or procedural requirements, administrative reasons requiring cessation of treatment, or until the participant has received 17 cycles of study treatment (approximately 1 year). Each cycle is 3 weeks long.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features.

- Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment.

- Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment.

- Has intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:

1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0

2. High risk RCC: pT4, Any Grade N0, M0; pT, Any stage, Any Grade, N+, M0

3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous).

- Has received no prior systemic therapy for advanced RCC.

- Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins.

- Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization.

- Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization.

- Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available).

- Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.

- Has adequate organ function.

Exclusion Criteria:

- Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization.

- Has received prior radiotherapy for RCC.

- Has pre-existing brain or bone metastatic lesions.

- Has residual thrombus post nephrectomy in the vena renalis or vena cava.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.

- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed.

- Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy.

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

- Has an active infection requiring systemic therapy.

- Has a history of, or is currently on, dialysis.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has known active hepatitis B or hepatitis C virus infection.

- Has a known history of active tuberculosis (Bacillus tuberculosis).

- Has had a prior solid organ transplant.

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

- Is pregnant or breastfeeding, or 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 received prior therapy with an anti-programmed cell death protein 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 co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.

- Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered agents.

- Has received a live vaccine within 30 days prior to the first dose of study treatment.

- 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.

Studien-Rationale

Primary outcome:

1. Disease-free Survival (DFS) as Assessed by the Investigator (Time Frame - Up to approximately 72 months):
DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first.



Secondary outcome:

1. Overall Survival (OS) (Time Frame - Up to approximately 72 months):
OS is defined as the time from randomization to death due to any cause.

2. Adverse Events (AEs) (Time Frame - Nonserious AEs: Up to 30 days after last dose of study treatment (Up to approximately 13 months); Serious AEs: Up to 90 days after last dose of study treatment (Up to approximately 15 months)):
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Participants are monitored for the occurrence of nonserious AEs for up to 30 days after last dose of study treatment and of serious AEs for up to 90 days after last dose of study treatment. The number of participants who experience an AE will be assessed.

3. Study Treatment Discontinuations Due to an AE (Time Frame - Up to approximately 12 months):
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who discontinue study treatment due to an AE will be assessed.

4. First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator (Time Frame - Up to approximately 72 months):
DRSS1 is defined as the time from randomization to the first documented local recurrence of RCC as assessed by the investigator. For DRSS1, only local recurrence is counted as an event.

5. First Local Recurrence with Visceral Lesion or Distant Metastasis with Visceral Lesion or Secondary Systemic Malignancy with Visceral Lesion (DRSS2) as Assessed by the Investigator (Time Frame - Up to approximately 72 months):
DRSS2 is defined as the time from randomization to the first documented local recurrence with visceral lesion or distant metastasis with visceral lesion or secondary systemic malignancy with visceral lesion, whichever occurs first, as assessed by the investigator. For DRSS2, only disease recurrence with visceral lesion is counted as an event.

6. DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator (Time Frame - Up to approximately 72 months):
DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first.

7. OS According to Participant PD-L1 Expression Status (Positive, Negative) (Time Frame - Up to approximately 72 months):
OS is defined as the time from randomization to death due to any cause.

8. Plasma Clearance (CL) of Pembrolizumab (Time Frame - Cycles 1 and 2: Pre-dose and 0.5 hours (h) after end of infusion; Cycles 3, 5, 13 and 17: Pre-dose; and 30 days after study treatment discontinuation. Each cycle is 3 weeks long. (Up to approximately 13 months)):
CL is the volume of plasma from which a substance is completely removed per unit time.

9. Volume of Distribution (VD) of Pembrolizumab (Time Frame - Cycles 1 and 2: Pre-dose and 0.5 h after end of infusion; Cycles 3, 5, 13 and 17: Pre-dose; and 30 days after study treatment discontinuation. Each cycle is 3 weeks long. (Up to approximately 13 months)):
The VD of a drug represents the degree to which a drug is distributed in body tissue rather than the plasma. VD is directly correlated with the amount of drug distributed into tissue; a higher VD indicates a greater amount of tissue distribution.

10. Development of Anti-pembrolizumab Antibodies (Time Frame - Cycles 1, 3, 5, 13 and 17: Pre-dose; and 30 days after study treatment discontinuation. Each cycle is 3 weeks long. (Up to approximately 13 months)):
The number of participants who develop serum anti-pembrolizumab antibodies will be presented.

11. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score (Time Frame - Baseline and Cycles 1, 5, 9, 13, and 17, treatment discontinuation, 30 day follow up, and annually during post-treatment follow up. Each cycle is 3 weeks long. (Up to approximately 72 months)):
The QLQ-C30 quality of life (QOL) questionnaire contains 5 functioning scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain) and single symptom items (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Items are scored on a 4-point scale (1=not at all, 2=a little, 3= quite a bit, 4=very much). The QLQC30 also contains 2 global health status scales that use 7-point scale scoring (1=very poor and 7=excellent). The change from baseline in the 2-item global health status/QOL life scale (range: 2-14) will be presented, with a higher score representing a higher QOL.

12. Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score (Time Frame - Baseline and Cycles 1, 5, 9, 13, and 17, treatment discontinuation, 30 day follow up, and annually during post-treatment follow up. Each cycle is 3 weeks long. (Up to approximately 72 months)):
The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status.

Studien-Arme

  • Experimental: Pembrolizumab
    Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles.
  • Placebo Comparator: Placebo
    Participants receive placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles.

Geprüfte Regime

  • Pembrolizumab (MK-3475):
    IV infusion
  • Placebo (saline solution) (saline solution):
    IV infusion

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren

„Durch Wissen zum Leben“

Wann immer möglich, wird heutzutage versucht, Krebspatienten Klinikaufenthalte zu ersparen. Die Behandlung erfolgt vielmehr bevorzugt ambulant bei niedergelassenen Krebsmedizinern oder in Klinikambulanzen. Das erlaubt es den Patienten, trotz der Erkrankung weitestgehend in ihrer gewohnten Umgebung zu leben und ihrem Alltag nachgehen zu können. Die vorwiegend ambulante Behandlung hat jedoch auch zur Folge, dass dem Patienten weniger Ansprechpartner zu allen Fragen zur Erkrankung und...

Heller Hautkrebs: Signalweg entschlüsselt

Beim Hautkrebs gibt es verschiedene Krankheitsformen: Mit Abstand am häufigsten ist dabei das so genannte Basalzellkarzinom, eine Form von hellem Hautkrebs, bei der sich der Tumor von seinem Entstehungsort in der Haut langsam aber stetig ausbreitet. Zwar bildet das Basalzellkarzinom im Allgemeinen keine Tochtergeschwülste (Metastasen), der Tumor sollte jedoch so früh wie möglich behandelt werden, da er ansonsten das umgebende Gewebe zerstören und sogar Muskeln...

Neue Perspektiven für Frauen mit Eierstockkrebs

In der medikamentösen Behandlung von Frauen mit fortgeschrittenem Eierstockkrebs wurde erstmals nach fast 15 Jahren ein Fortschritt erzielt: Das neue Medikament, ein sogenannter Angiogenesehemmer, greift den Tumor gezielt an und verzögert damit das Fortschreiten der Krebserkrankung. Für die betroffenen Frauen ist dies ein großer Vorteil: Die Therapie ermöglicht ihnen mehr Zeit, die sie – trotz der schweren Erkrankung – weitestgehend beschwerdefrei...