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JOURNAL ONKOLOGIE – STUDIE

Efficacy and Safety Study of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Adults With Medically Inoperable Stage I or IIA Non-Small Cell Lung Cancer (NSCLC) (MK-3475-867/KEYNOTE-867)

Rekrutierend

NCT-Nummer:
NCT03924869

Studienbeginn:
Juni 2019

Letztes Update:
19.01.2021

Wirkstoff:
Pembrolizumab, Placebo

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

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 144)

Sanford Bemidji ( Site 0080)
56601 Bemidji
United StatesAbgeschlossen» Google-Maps
IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0208)
C1012AAR Buenos Aires
ArgentinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: (+54 911) 4162-5353
» Ansprechpartner anzeigen
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0301)
90610-000 Porto Alegre
BrazilRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +555133203039
» Ansprechpartner anzeigen
GUZ Lipetsk Regional Oncology Dispensary ( Site 2010)
398005 Lipetsk
Russian FederationAbgeschlossen» Google-Maps
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 2000)
197758 Saint-Petersburg
Russian FederationRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +79111005005
» Ansprechpartner anzeigen
Kartal Training and Research Hospital ( Site 2102)
34890 Istanbul
TurkeyAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to assess the efficacy and safety of stereotactic body

radiotherapy (SBRT) plus pembrolizumab (MK-3475) in the treatment of adult participants with

medically inoperable Stage I or IIA non-small cell lung cancer (NSCLC).

The primary study hypotheses are:

1. SBRT plus pembrolizumab prolongs Event-free Survival (EFS) compared to SBRT plus placebo

(normal saline solution), and

2. SBRT plus pembrolizumab prolongs Overall Survival (OS) compared to SBRT plus placebo.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has previously untreated NSCLC diagnosed by histology or cytology and confirmed as

Stage I or IIA NSCLC (American Joint Committee on Cancer, AJCC) by chest computed

tomography (CT) and positron emission tomography (PET) scan

- Cannot undergo thoracic surgery due to existing medical illness(es) as determined by

the site's multi-disciplinary tumor board

- Has a Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

- Is able to receive SBRT and does not have an ultra-centrally located tumor

- Has adequate organ function within 7 days prior to the start of study treatment

- A female is eligible to participate if she is not pregnant, not breastfeeding, and at

least one of the following conditions applies: a) not a women of childbearing

potential (WOCBP) OR b) A WOCBP who agrees to use study-acceptable contraception

during treatment and for at least 120 days after last dose of study treatment

Exclusion Criteria:

- Has received prior therapy with an anti-programmed cell death-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 (e.g. cytotoxic

T-lymphocyte-associated antigen 4 [CTLA-4], tumor necrosis factor receptor superfamily

member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137])

- Has received prior radiotherapy to the thorax, including radiotherapy to the

esophagus, mediastinum, or breast

- 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. Note: Participants who have entered the follow-up phase of an

investigational study may participate as long as it has been 4 weeks after the last

dose of the previous investigational agent

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

within the past 3 years. Note: Participants with basal cell carcinoma of the skin,

squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma,

cervical cancer in situ) that have undergone potentially curative therapy are not

excluded.

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

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

pneumonitis

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

- 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). However, replacement therapy (e.g. thyroxine, insulin, or physiologic

corticosteroid replacement therapy for adrenal or pituitary insufficiency), while

systemic, will be permitted for study eligibility.

- Has an active infection requiring systemic therapy

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

- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

- 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 had an allogenic tissue/solid organ transplant

Studien-Rationale

Primary outcome:

1. Event-free Survival (EFS) (Time Frame - Up to approximately 6 years):
EFS is defined as the time from randomization to the first occurrence of any of the following events: Local, regional, or distant recurrence of disease as assessed by: Radiographic recurrence by blinded independent central review (BICR) Positive pathology by local assessment Physical examination by local assessment confirmed by positive pathology and/or radiographic recurrence by BICR OR Death due to any cause. EFS will be presented.

2. Overall Survival (OS) (Time Frame - Up to approximately 6 years):
OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.

Secondary outcome:

1. Time to Death or Distant Metastases (TDDM) (Time Frame - Up to approximately 6 years):
TTDM is defined as the time from randomization to the first documented distant metastases or death from any cause, whichever occurs first. The TDDM will be presented.

2. Number of Participants Who Experience an Adverse Event (AE) (Time Frame - Up to approximately 6 years):
An AE is 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 an AE will be presented.

3. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) (Time Frame - Up to approximately 6 years):
An AE is 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.

4. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score (Time Frame - Baseline and up to approximately 52 weeks):
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall outcome. The change from baseline in Global Health Status/Quality of Life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.

5. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Cough (Item 31) Score (Time Frame - Baseline and up to approximately 52 weeks):
The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in cough (EORTC QLQ LC13 Item 31) score will be presented.

6. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Chest Pain (Item 10) Score (Time Frame - Baseline and up to approximately 52 weeks):
The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score will be presented.

7. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score (Time Frame - Baseline and up to approximately 52 weeks):
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented.

8. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score (Time Frame - Baseline and up to approximately 52 weeks):
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.

Studien-Arme

  • Experimental: SBRT+Pembolizumab
    Participants receive SBRT once every 3 days for 3-5 fractions (dependent on tumor type/location; 45-54 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.
  • Placebo Comparator: SBRT+Placebo
    Participants receive SBRT once every 3 days for 3-5 fractions (dependent on tumor type/location; 45-54 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.

Geprüfte Regime

  • Stereotactic Body Radiotherapy (SBRT):
    SBRT
  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    IV infusion
  • Placebo (Normal saline solution):
    IV infusion

Quelle: ClinicalTrials.gov


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