A Phase III study with Pembrolizumab or placebo as adjuvant therapy in patients with liver cancer who have completely responded to surgical resection or local ablation of the tumor.
Descrizione riassuntiva dello studio
The immune system plays an important role in tumor control. Pembrolizumab is an antibody that can inhibit immune suppression by the tumor and thus enhance the body's natural fight against it. The study investigates the adjuvant (supportive) effect of Pembrolizumab compared to a placebo (dummy drug, containing no active substance) after complete surgical resection of a liver tumor of stage IB, II, or III. The aim is to find out whether Pembrolizumab can delay or even prevent the recurrence of cancer. The total duration of the study is approximately 7 years. Participants will be treated with the study medication for approximately 1 year, followed by a follow-up phase.
(BASEC)
Intervento studiato
Approximately 950 patients are expected to participate in this study.
After a thorough eligibility assessment, collection of medical history, and detailed explanation, the participant will be included in the study and randomly assigned to one of the two treatment arms (Pembrolizumab or placebo). The probability of being assigned to the Pembrolizumab treatment group is 50%. Neither the study physician nor the participant knows the assignment and thus the treatment applied (the study is referred to as "double-blind"). In case of an emergency, however, the study physician may learn the assignment.
Participants receive intravenous Pembrolizumab or placebo (depending on the assigned group) every three weeks for 17 cycles (approximately 1 year). During this period, their health status will be regularly monitored for any recurrence of cancer using imaging studies.
After completion of treatment or after discontinuation of treatment for reasons other than the recurrence of cancer, participants will enter the follow-up phase, where they will be monitored every 3 months for the first 3 years, every 6 months in the fourth and fifth years, and every 12 months in the sixth and seventh years.
During the study visits, various measures and examinations may take place:
Discussion of health status and current medication, intravenous therapy, imaging procedures (CT and/or MRI scans), electrocardiogram (ECG), samples of blood, urine, or tissue, questionnaires, and monitoring of vital signs (pulse, blood pressure, etc.).
Should the disease recur, the study participant will be contacted by the study team approximately every 12 weeks or more frequently to inquire about their health status.
(BASEC)
Malattie studiate
Participants in the study are patients whose liver tumor has been surgically removed or ablated locally at stage IB, II, or III prior to the start of the study. Treatment within the study must begin within 12 weeks after tumor removal. Clinical research data show that this population has a medical need for supportive therapy after surgical removal of the tumor, as it is not uncommon for a new tumor to form. The aim of this study with the so-called adjuvant therapy is to investigate whether the recurrence of the disease can be delayed and whether the survival rate can be increased.
(BASEC)
• Adult male or female individuals whose liver tumor has been completely removed by surgery or local ablation within 6 weeks of staging, and for whom the probability of tumor recurrence is medium, high, or very high. • The complete removal of the tumor must have been confirmed radiologically (by CT or MRI) after ≥ 4 weeks, and the person must have fully recovered from the surgery or local ablation. • No more than 12 weeks should elapse between the complete surgical removal of the liver tumor and the first study treatment. (BASEC)
Criteri di esclusione
• Individuals with another known malignant cancer that is progressing or that required active antineoplastic therapy (including hormonal therapy) or surgical intervention within the last 3 years. • Individuals for whom local ablation was performed using a method other than radiofrequency or microwave ablation. • Individuals who have already received certain immunotherapies or systemic cancer therapy for liver cancer, or who are currently receiving another medical treatment such as systemic chemotherapy, radiation therapy, oncological surgical therapy, other study medications, immunotherapies, or systemic glucocorticoids. (BASEC)
Luogo dello studio
Basilea, Berna, Ginevra, Losanna, San Gallo, Winterthur, Zurigo
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG Luzern
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Klaudia Georgi
+41 68 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG Werftestrasse 4 CH-6005 Luzern
(BASEC)
Informazioni generali
Merck Sharp & Dohme LLC
(ICTRP)
Informazioni scientifiche
Merck Sharp & Dohme LLC
(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
28.05.2019
(BASEC)
ID di studio ICTRP
NCT03867084 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) versus Placebo as Adjuvant Therapy in Participants with Hepatocellular Carcinoma and Complete Radiological Response after Surgical Resection or Local Ablation (KEYNOTE-937) (BASEC)
Titolo accademico
A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma and Complete Radiological Response After Surgical Resection or Local Ablation (KEYNOTE-937) (ICTRP)
Titolo pubblico
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) (ICTRP)
Malattie studiate
Hepatocellular Carcinoma (ICTRP)
Intervento studiato
Biological: PembrolizumabDrug: Placebo (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Criteri di inclusione/esclusione
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/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
- 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. (ICTRP)
non disponibile
Endpoint primari e secondari
Recurrence-Free Survival (RFS);Overall Survival (OS) (ICTRP)
Percentage of Participants who Experience an Adverse Event (AE);Percentage of Participants who Discontinue Study Treatment Due to an AE;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;Change from Baseline in EORTC QLQ-C30 Physical Functioning Scale Score;Change from Baseline in EORTC QLQ-C30 Role Functioning Scale Score;Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Abdominal Swelling Scale Score;Change from Baseline in EORTC QLQ-HCC18 Fatigue Scale Score;Change from Baseline in EORTC QLQ-HCC18 Pain Scale Score;Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score;Time to Deterioration (TTD) in the EORTC QLQ-C30 Combined GHS / QoL Scale Score;TTD in the EORTC QLQ-C30 Physical Functioning Scale Score;TTD in the EORTC QLQ-C30 Role Functioning Scale Score;TTD in the EORTC QLQ-HCC18 Abdominal Swelling Scale Score;TTD in the EORTC QLQ-HCC18 Fatigue Scale Score;TTD in the EORTC QLQ-HCC18 Pain Scale Score (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
ID secondari
MK-3475-937, KEYNOTE-937, 194786, 2022-501971-24-00, U1111-1282-6370, 2018-004800-20, 3475-937 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT03867084 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile