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Trial record 1 of 1 for:    03924869
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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)

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ClinicalTrials.gov Identifier: NCT03924869
Recruitment Status : Recruiting
First Posted : April 23, 2019
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Radiation: Stereotactic Body Radiotherapy (SBRT) Biological: Pembrolizumab Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 530 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Participants With Medically Inoperable Stages I or IIA Non Small Cell Lung Cancer (NSCLC) (KEYNOTE-867)
Actual Study Start Date : June 25, 2019
Estimated Primary Completion Date : April 11, 2025
Estimated Study Completion Date : July 1, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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.
Radiation: Stereotactic Body Radiotherapy (SBRT)
SBRT

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

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.
Radiation: Stereotactic Body Radiotherapy (SBRT)
SBRT

Drug: Placebo
IV infusion
Other Name: Normal saline solution




Primary Outcome Measures :
  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 Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has 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 participant's treating physician in consultation with 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
  • 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 treatment (pembrolizumab)

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03924869


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 30 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03924869     History of Changes
Other Study ID Numbers: 3475-867
MK-3475-867 ( Other Identifier: Merck )
2018-004320-11 ( EudraCT Number )
KEYNOTE-867 ( Other Identifier: Merck )
194909 ( Registry Identifier: JAPAC-CTI )
First Posted: April 23, 2019    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents