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JOURNAL ONKOLOGIE – STUDIE

KEYNOTE-966 Pembrolizumab (MK-3475) Plus Gemcitabine/Cisplatin Versus Placebo Plus Gemcitabine/Cisplatin for First-Line Advanced and/or Unresectable Biliary Tract Carcinoma (BTC) (MK-3475-966/KEYNOTE-966)

Rekrutierend

NCT-Nummer:
NCT04003636

Studienbeginn:
September 2019

Letztes Update:
25.09.2020

Wirkstoff:
Pembrolizumab, Gemcitabine, Cisplatin, Placebo

Indikation (Clinical Trials):
Carcinoma

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 153)

Osaka International Cancer Institute ( Site 0084)
541-8567 Osaka
JapanAbgeschlossen» Google-Maps
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Studien-Informationen

Brief Summary:

This is a study of pembrolizumab plus gemcitabine/cisplatin versus placebo plus gemcitabine/cisplatin as first-line therapy in participants with advanced and/or unresectable biliary tract carcinoma. The study has 2 primary hypotheses: 1. Pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by blinded independent central review (BICR) and 2. Pembrolizumab plus gemcitabine/cisplatin is superior to placebo plus gemcitabine/cisplatin with respect to overall survival (OS).

Ein-/Ausschlusskriterien

Inclusion Criteria

- Has histologically confirmed diagnosis of advanced (metastatic) and/or unresectable (locally advanced) biliary tract cancer (intra-or extrahepatic cholangiocarcinoma or gallbladder cancer)

- Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1), as determined by the site investigator

- Participants with a history of hepatitis B or hepatitis C can be enrolled if they meet study criteria

- Is able to provide archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion

- Has a life expectancy of greater than 3 months

- Has adequate organ function

Exclusion Criteria

- Has had previous systemic therapy for advanced (metastatic) or unresectable (locally advanced) biliary tract cancer (intra-or extra hepatic cholangiocarcinoma or gallbladder cancer), with the exception of adjuvant therapy which is allowed

- Has ampullary cancer

- Has small cell cancer, neuroendocrine tumors, lymphoma, sarcoma, mixed tumor histology and/or mucinous cystic neoplasms

- Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti- programmed cell death ligand 1 or 2 (anti-PD-L1, 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 a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis, as assessed by local site investigator

- Has had an allogenic tissue/solid organ transplant

Studien-Rationale

Primary outcome:

1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR) (Time Frame - Up to 48 months):
Progression-free survival is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Progressive Disease (PD) is a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of ≥20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

2. Overall Survival (OS) (Time Frame - Up to 48 months):
Overall survival is defined as the time from randomization to death due to any cause.

Secondary outcome:

1. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR (Time Frame - Up to 48 months):
ORR is defined as the percentage of participants who have a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: a ≥30% decrease in the sum of diameters [SOD] of target lesions) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

2. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR (Time Frame - Up to 48 months):
For participants who demonstrate confirmed CR or PR, DOR is the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. Complete Response is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is a ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is a ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of ≥20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

3. Number of Participants Who Experience One or More Adverse Events (AE) (Time Frame - Up to 48 months):
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

4. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (Time Frame - Up to 48 months):
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.

Studien-Arme

  • Experimental: Arm A (Pembrolizumab+Gemcitabine+Cisplatin)
    Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.
  • Placebo Comparator: Arm B (Placebo+Gemcitabine+Cisplatin)
    Placebo to Pembrolizumab, 200 mg, every 3 weeks (Q3W), Day 1 of each 3-week cycle for up to 35 cycles PLUS Gemcitabine, 1000 mg/m^2, Q3W, Day 1 and Day 8 of each cycle until progressive disease or unacceptable toxicity PLUS Cisplatin, 25 mg/m^2, Q3W, Day 1 and Day 8 of each cycle for up to 8 cycles.

Geprüfte Regime

  • Pembrolizumab (MK-3475):
    Pembrolizumab by intravenous (IV) infusion
  • Gemcitabine (Gemzar):
    Gemcitabine by IV infusion
  • Cisplatin (Platinol® / Platinol®-AQ / ):
    Cisplatin by IV infusion
  • Placebo:
    Placebo to pembrolizumab

Quelle: ClinicalTrials.gov


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