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JOURNAL ONKOLOGIE – STUDIE

Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)

Rekrutierend

NCT-Nummer:
NCT03221426

Studienbeginn:
Oktober 2017

Letztes Update:
19.03.2019

Wirkstoff:
Placebo, Capecitabine, Docetaxel, Oxaliplatin, Cisplatin, Leucovorin, 5-Fluorouracil, Pembrolizumab

Indikation (Clinical Trials):
Adenocarcinoma, Stomach Neoplasms

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 143)

Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 0454)
20249 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49404602001
» Ansprechpartner anzeigen
Medizinische klinilk und Poliklinik Johannes Gutenberg Univ ( Site 0455)
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +496131176076
» Ansprechpartner anzeigen
Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0018)
60611 Chicago
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 312-695-6180
» Ansprechpartner anzeigen
University of Utah, Huntsman Cancer Institute ( Site 0012)
84112 Salt Lake City
United StatesAbgeschlossen» Google-Maps
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0308)
90610-000 Porto Alegre
BrazilRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +555133203039
» Ansprechpartner anzeigen
Hospital Clinico Universidad de Chile ( Site 0287)
8380456 Santiago
ChileAbgeschlossen» Google-Maps
Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0354)
43-300 Bielsko-Biala
PolandAbgeschlossen» Google-Maps
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0344)
197758 Saint Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79219462123
» Ansprechpartner anzeigen
The Christie NHS Foundation Trust ( Site 0397)
M20 4BX Manchester
United KingdomAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS), event-free survival (EFS) and pathological complete response (pathCR) rate.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.

- Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.

- Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.

- Has adequate organ function.

- Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.

- Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.

- Has life expectancy of greater than 6 months.

Exclusion Criteria:

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

- Has an active infection requiring systemic therapy.

- Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first 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 stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.

- Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.

- 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 14 days prior the first dose of study treatment.

- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.

- Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.

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

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

- Has a known history of Hepatitis B or known active Hepatitis C virus infection.

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

- Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.

- Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.

- Has had an allogenic tissue/solid organ transplant.

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

Studien-Rationale

Primary outcome:

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

2. Event-free Survival (EFS) (Time Frame - Up to approximately 2 years):
EFS is defined as the time from randomization to the first of the following events: radiographic disease progression per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1); local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); or death due to any cause. A second primary malignancy is not considered as an EFS event.

3. Pathological Complete Response (pathCR) Rate (Time Frame - Up to 6 weeks after completion of 3 cycles of neoadjuvant treatment (Up to 15 weeks)):
PathCR rate is defined as the percentage of participants having pathCR. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes.

4. Adverse Events (AEs) (Time Frame - Up to approximately 27 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. The number of participants who experience at least one AE will be presented.

5. Study Treatment Discontinuations Due to AEs (Time Frame - Up to approximately 2 years):
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. The number of participants who discontinue study treatment due to an AE will be presented.

Secondary outcome:

1. Disease-free Survival (DFS) (Time Frame - Up to approximately 2 years):
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local/distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by blinded independent central review.

Studien-Arme

  • Experimental: Pembrolizumab+Chemotherapy
    Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 14 cycles.
  • Placebo Comparator: Placebo+Chemotherapy
    Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU via continuous IV infusion on Days 1 to 5 of each 3-week cycle for up to 14 cycles.
  • Experimental: Pembrolizumab+FLOT Safety Cohort
    FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations. Adjuvant: 4 to 10 weeks postsurgery, participants receive pembrolizumab 200 mg via IV infusion Day 1 Q3W for up to 11 cycles PLUS docetaxel 50 mg/m^2, oxaliplatin 85 mg/m^2, 5FU 2600 mg/m^2, and leucovorin 200 mg/m^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.
  • Placebo Comparator: Placebo+FLOT Safety Cohort
    Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations. Adjuvant: 4 to 10 weeks postsurgery, participants receive placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3) for 4 administrations.

Geprüfte Regime

  • Pembrolizumab (MK-3475):
    IV infusion
  • Placebo (Normal saline solution):
    Normal saline solution IV infusion
  • Cisplatin (PLATINOL®):
    IV infusion
  • Capecitabine (XELODA®):
    Oral tablets
  • 5-fluorouracil (ADRUCIL® / 5FU / ):
    IV infusion
  • Docetaxel (TAXOTERE®):
    IV infusion
  • Oxaliplatin (ELOXATIN®):
    IV infusion
  • Leucovorin (WELLCOVORIN®):
    IV infusion

Quelle: ClinicalTrials.gov


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