Samstag, 15. Mai 2021
Navigation öffnen
Anzeige:
Darzalex
Darzalex
 
JOURNAL ONKOLOGIE – STUDIE

Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)

Rekrutierend

NCT-Nummer:
NCT03867084

Studienbeginn:
Mai 2019

Letztes Update:
14.05.2021

Wirkstoff:
Pembrolizumab, Placebo

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular

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 231)

SLK-Kliniken Heilbronn GmbH ( Site 0460)
74078 Heilbronn
(Baden-Württemberg)
GermanyAbgeschlossen» Google-Maps
Universitaetsklinikum Tuebingen ( Site 0466)
72076 Tuebingen
(Baden-Württemberg)
GermanyAbgeschlossen» Google-Maps
Universitaetsklinikum Koeln ( Site 0463)
50937 Koeln
(Nordrhein-Westfalen)
GermanyAbgeschlossen» Google-Maps
University Medical Center New Orleans ( Site 0014)
70112 New Orleans
United StatesAbgeschlossen» Google-Maps
McGill University Health Centre ( Site 0207)
H4A 3J1 Montreal
CanadaAktiv, nicht rekrutierend» Google-Maps
A O U Policlinico di Modena ( Site 0548)
41025 Modena
ItalyAbgeschlossen» Google-Maps
Istituto Tumori Giovanni Paolo II ( Site 0543)
70124 Bari
ItalyAbgeschlossen» Google-Maps
Ehime University Hospital ( Site 0123)
791-0204 Toon
JapanAktiv, nicht rekrutierend» Google-Maps
Kurume University Hospital ( Site 0119)
830-0011 Kurume
JapanAktiv, nicht rekrutierend» Google-Maps
Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0102)
060-0033 Sapporo
JapanAktiv, nicht rekrutierend» Google-Maps
Kanazawa University Hospital ( Site 0111)
920-8641 Kanazawa
JapanAktiv, nicht rekrutierend» Google-Maps
Kagawa University Hospital ( Site 0121)
761-0793 Kita-gun
JapanAktiv, nicht rekrutierend» Google-Maps
Toranomon Hospital Kajigaya ( Site 0109)
213-8587 Kawasaki
JapanAktiv, nicht rekrutierend» Google-Maps
Yokohama City University Medical Center ( Site 0110)
232-0024 Yokohama
JapanAktiv, nicht rekrutierend» Google-Maps
Saitama Medical University Hospital ( Site 0104)
350-0495 Iruma-gun
JapanAktiv, nicht rekrutierend» Google-Maps
Kyorin University Hospital ( Site 0106)
181-8611 Mitaka
JapanAktiv, nicht rekrutierend» Google-Maps
Musashino Red Cross Hospital ( Site 0107)
180-8610 Musashino
JapanAktiv, nicht rekrutierend» Google-Maps
Chiba University Hospital ( Site 0103)
260-8677 Chiba
JapanAktiv, nicht rekrutierend» Google-Maps
National Hospital Organization Kyushu Medical Center ( Site 0118)
810-8563 Fukuoka
JapanAktiv, nicht rekrutierend» Google-Maps
Hiroshima University Hospital ( Site 0117)
734-8551 Hiroshima
JapanAktiv, nicht rekrutierend» Google-Maps
University Hospital, Kyoto Prefectural University of Medicine ( Site 0112)
602-8566 Kyoto
JapanAktiv, nicht rekrutierend» Google-Maps
Japanese Red Cross Osaka Hospital ( Site 0113)
543-8555 Osaka
JapanAktiv, nicht rekrutierend» Google-Maps
Saga-Ken Medical Centre Koseikan ( Site 0120)
840-8571 Saga
JapanAktiv, nicht rekrutierend» Google-Maps
Toranomon Hospital ( Site 0108)
105-8470 Tokyo
JapanAktiv, nicht rekrutierend» Google-Maps
The University of Tokyo Hospital ( Site 0105)
113-8655 Tokyo
JapanAktiv, nicht rekrutierend» Google-Maps
Wakayama Medical University Hospital ( Site 0115)
641-8510 Wakayama
JapanAktiv, nicht rekrutierend» Google-Maps
Izerskie Centrum Pulmonologii i Chemioterapii IZER-MED Spolka z o.o. ( Site 0607)
58-580 Szklarska Poreba
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +48757547148
» Ansprechpartner anzeigen
City Clinical Hospital 1 na. NI. Pirogov ( Site 0662)
119049 Moscow
Russian FederationAbgeschlossen» Google-Maps
Samara Regional Clinical Oncology Center ( Site 0656)
443031 Samara
Russian FederationAbgeschlossen» Google-Maps
Road Hospital JSC Russian railways ( Site 0649)
195271 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
Russian Scientific Center of Radiology and Surgical Technologies ( Site 0665)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 79213182207
» Ansprechpartner anzeigen
Tomsk Scientific Research Institute of Oncology ( Site 0657)
634028 Tomsk
Russian FederationAbgeschlossen» Google-Maps
Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0335)
833 Kaohsiung
TaiwanAbgeschlossen» Google-Maps
Namik Kemal Universitesi Tip Fakultesi ( Site 0738)
59100 Tekirdag
TurkeyAbgeschlossen» Google-Maps
Adnan Menderes University Medical Faculty ( Site 0737)
09010 Aydin
TurkeyAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This study will evaluate the safety and efficacy of pembrolizumab (MK-3475) versus placebo as

adjuvant therapy in participants with hepatocellular carcinoma (HCC) and complete

radiological response after surgical resection or local ablation. The primary hypotheses of

this study are that adjuvant pembrolizumab is superior to placebo with respect to: 1)

recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and

2) overall survival (OS).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has a diagnosis of HCC by radiological criteria and/or pathological confirmation.

- Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and

CT or MRI of the pelvis) confirming complete radiological response ≥4 weeks after

complete surgical resection or local ablation. Randomization needs to occur within 12

weeks of the date of surgical resection or local ablation.

- Has no radiologic evidence of disease prior to enrollment.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7

days prior to Cycle 1, Day 1.

- Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1,

Day 1.

- Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to

Cycle 1, Day 1.

- Has controlled hepatitis B (Hep B).

- Has recovered adequately from toxicity and/or complications from the local

intervention (surgical resection or local ablation) prior to starting study treatment.

- If female, is not pregnant or breastfeeding, and at least one of the following

conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a

WOCBP and using a contraceptive method that is highly effective or be abstinent from

heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a

negative pregnancy test within 72 hours before the first dose of study treatment).

- If undergoing surgical resection, has submitted a tumor tissue sample during

Screening.

- Has adequate organ function.

Exclusion Criteria:

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

antineoplastic treatment (including hormonal) or surgery within the past 3 years.

- Has had esophageal or gastric variceal bleeding within the last 6 months.

- Has clinically apparent ascites on physical examination.

- Has had clinically diagnosed hepatic encephalopathy in the last 6 months.

- Has received local therapy to liver ablation other than with radiofrequency or

microwave ablation.

- Has a history of (noninfectious) pneumonitis that required steroids or has current

pneumonitis.

- Has an active infection requiring systemic therapy.

- Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study

entry.

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

- Has known active tuberculosis (TB; Bacillus tuberculosis).

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with

an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,

OX-40, CD137).

- Has received prior systemic anti-cancer therapy for HCC including investigational

agents.

- Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic

systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this

protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5)

Oncological surgical therapy; or systemic glucocorticoids for any purpose other than

to modulate symptoms from an AE that is suspected to have an immunologic etiology.

- 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 Cycle 1, Day 1.

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

or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.

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

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

- Has a known psychiatric or substance abuse disorder that would interfere with the

participant's ability to cooperate with the requirements of the study.

- Has had an allogenic tissue/solid organ transplant.

Studien-Rationale

Primary outcome:

1. Recurrence-Free Survival (RFS) (Time Frame - Up to ~4 years):
RFS is defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by BICR or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death), whichever occurs first.

2. Overall Survival (OS) (Time Frame - Up to ~6 years):
OS is defined as the time from randomization to death due to any cause.

Secondary outcome:

1. Percentage of Participants who Experience an Adverse Event (AE) (Time Frame - Up to ~6 years):
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

2. Percentage of Participants who Discontinue Study Treatment Due to an AE (Time Frame - Up to ~1 year):
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

3. Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score (Time Frame - Baseline and time of last patient reported outcome (PRO) assessment (up to ~7 years)):
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients, including a combined GHS/QoL (Items 29 and 30) scale. Per protocol, the change from baseline in the combined GHS/QoL score (range: 0-100) will be reported. Higher overall GHS/QoL scores indicate higher GHS/QoL.

4. Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score (Time Frame - Baseline and time of last PRO assessment (up to ~7 years)):
The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30, with scores ranging from 0-100. Higher scores indicate more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 scale score will be reported.

5. Time to Deterioration (TTD) in the EORTC-QLQ-C30, Combined GHS / QoL Scale Score (Time Frame - Time of last PRO assessment (up to ~7 years)):
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Per protocol, the TTD in the combined GHS/QoL scale score will be reported, defined as the time to first onset of a ≥10 point decrease from baseline.

6. Time to Deterioration (TTD) in the EORTC QLQ-HCC18 Scale Score (Time Frame - Time of last PRO assessment (up to ~7 years)):
The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30. The TTD in EORTC QLQ-HCC18 scale score will be reported, defined as the time to first onset of a ≥10 point decrease from baseline.

7. Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score (Time Frame - Baseline and time of last PRO assessment (up to ~7 years)):
The EQ-5D-5L measured health-related outcomes, assessing 5 health state dimensions (mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression) on a 5-point scale from 1 (no problem) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health.

Studien-Arme

  • Experimental: Pembrolizumab
    Participants receive intravenous (IV) pembrolizumab at 200 mg on Day 1 of each 21-day cycle for up to 17 cycles.
  • Placebo Comparator: Placebo
    Participants receive IV placebo on Day 1 of each 21-day cycle for up to 17 cycles.

Geprüfte Regime

  • Pembrolizumab (KEYTRUDA® / MK-3475 / ):
    IV infusion of Pembrolizumab 200 mg.
  • Placebo:
    IV infusion of 0.9% normal saline.

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
70 Prozent der Deutschen fürchten Tumor, Engagement für Gesundheit wächst
70+Prozent+der+Deutschen+f%C3%BCrchten+Tumor%2C+Engagement+f%C3%BCr+Gesundheit+w%C3%A4chst
© pressmaster / Fotolia.com

Sieben von zehn Menschen in Deutschland fürchten sich am meisten vor Krebs. Bei Erwachsenen zwischen 30 und 44 Jahren und Frauen ist die Angst besonders groß. Das zeigt eine aktuelle und repräsentative Studie der DAK-Gesundheit. Ein weiteres zentrales Ergebnis: Das Engagement für die eigene Gesundheit wächst. Immer mehr Menschen gehen zu Vorsorgeuntersuchungen und halten sich mit Sport und gesunder Ernährung fit.

Die P4-Medizin – Krebstherapie der Zukunft?
Die+P4-Medizin+%E2%80%93+Krebstherapie+der+Zukunft%3F
© Fotolia / psdesign1

Die Versorgung von krebskranken Menschen befindet sich in einem grundlegenden Wandel. Die Entwicklung neuer diagnostischer Methoden und individueller Therapien verändert die onkologische Medizin, wie wir sie bisher kennen. Das jüngst gewonnene Wissen über den Krebs und seine molekularbiologische Vielfalt verlangt nach neuen Antworten. In dem vom amerikanischen Biomediziner Leroy Hood geprägten Konzept der P4-Medizin wird...