ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Pembrolizumab (MK-3475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for Participants With Extensive Stage Small Cell Lung Cancer (MK-3475-604/KEYNOTE-604)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03066778
Recruitment Status : Recruiting
First Posted : February 28, 2017
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

The purpose of this study is to assess the safety and efficacy of pembrolizumab plus standard of care (SOC) chemotherapy (etoposide/platinum [EP]) in participants with newly diagnosed extensive stage small cell lung cancer (ES-SCLC) who have not previously received systemic therapy for this malignancy.

The primary study hypotheses are that pembrolizumab+EP prolongs Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review (BICR) and Overall Survival (OS) compared with placebo+EP in adult participants with ES-SCLC.


Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer SCLC Biological: Pembrolizumab Drug: Normal saline solution Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 430 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind, Placebo-controlled Trial of Pembrolizumab (MK-3475/SCH900475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for the First-line Treatment of Subjects With Extensive Stage Small Cell Lung Cancer (KEYNOTE-604)
Actual Study Start Date : May 2, 2017
Estimated Primary Completion Date : January 3, 2019
Estimated Study Completion Date : October 5, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Pembrolizumab+EP
During each 21-day cycle, participants receive pembrolizumab 200 mg intravenously (IV) Day 1 PLUS etoposide 100 mg/m^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an area under the plasma drug concentration-time curve [AUC] 5 IV on Day 1 OR cisplatin 75 mg/m^2 IV on Day 1).
Biological: Pembrolizumab
IV infusion on Day 1 of each cycle prior to chemotherapy
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion on Day 1 of each cycle
Other Name: PARAPLATIN®

Drug: Cisplatin
IV infusion on Day 1 of each cycle
Other Name: PLATINOL®

Drug: Etoposide
IV infusion on Days 1, 2 and 3 of each cycle
Other Name: TOPOSAR™

Active Comparator: Placebo+EP
During each 21-day cycle, participants receive placebo (normal saline solution) IV on Day 1 PLUS etoposide 100 mg/m^2 IV on Days 1, 2 and 3 PLUS investigator's choice of platinum (carboplatin titrated to an AUC 5 IV on Day 1 OR cisplatin 75 mg/m^2 IV on Day 1).
Drug: Normal saline solution
IV infusion on Day 1 of each cycle prior to chemotherapy

Drug: Carboplatin
IV infusion on Day 1 of each cycle
Other Name: PARAPLATIN®

Drug: Cisplatin
IV infusion on Day 1 of each cycle
Other Name: PLATINOL®

Drug: Etoposide
IV infusion on Days 1, 2 and 3 of each cycle
Other Name: TOPOSAR™




Primary Outcome Measures :
  1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 2 years ]
    PFS is defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered progression.

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


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 2 years ]
    ORR is defined as the percentage of participants who achieve a best objective response of Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions.

  2. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR [ Time Frame: Up to approximately 2 years ]
    For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.

  3. Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
    An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure.

  4. Percentage of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to approximately 2 years ]
    An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure.

  5. Percentage of Participants Experiencing Any Grade 3 to 5 AE as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE 4.0) [ Time Frame: Up to approximately 27 months ]
    Grade refers to the severity of the AE. The CTCAE uses Grades 1 through 5. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

  6. Change from Baseline at Weeks 12 and 24 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale [ Time Frame: Baseline and Week 12, Week 24 ]
    The QLQ-C30 quality of life (QOL) questionnaire contains 5 functioning scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea, and pain) and single symptom items (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Items are scored on a 4-point scale (1=not at all, 2=a little, 3= quite a bit, 4=very much). The QLQ-C30 also contains 2 global health status scales that use 7-point scale scoring (1=very poor and 7=excellent). The change from baseline in the 2-item global health status/QOL life scale (range: 2-14) will be presented, with a higher score representing a higher QOL.

  7. Time to True Deterioration in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the EORTC Quality of Life Questionnaire and Lung Cancer Module 13 (QLQ-LC13) [ Time Frame: Time frame: Day 1 of Cycles 1-9, Day 1 of every other cycle for Cycles 10-17 and 30 days after last dose of study treatment (Up to approximately 13 months) ]
    The EORTC QLQ-LC13, a supplemental lung cancer-specific module, consists of 13 multi-item and single-item measures of lung cancer-associated symptoms (i.e., coughing, hemoptysis, dyspnea, and pain) and side effects from chemotherapy and radiation (i.e., hair loss, neuropathy, sore mouth, and dysphagia). It is scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The results of the 6-item composite endpoint of cough, chest pain and dyspnea (range: 6-24) will be presented, with a higher score representing increasing symptom levels.



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.


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

Inclusion Criteria:

  • Has a documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration of a defined lesion. Participants who do not have histology samples (defined as core or excisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample.
  • Has extensive-stage disease defined as Stage IV (T any, N any, M 1a/b) by the American Joint Committee on Cancer (AJCC), Seventh Edition
  • Has ≥1 lesion that meets the criteria for measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator/radiology assessment
  • Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
  • Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Has a life expectancy of ≥3 months
  • Has adequate organ function
  • Female and male participants of childbearing potential must be willing to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of chemotherapeutic agents

Exclusion Criteria:

  • Has received prior systemic therapy for the treatment of SCLC
  • Is currently participating and receiving study treatment or has participated in a study of an investigational agent and received study treatment or used an investigational device within 4 weeks of the first dose of treatment for another health-related problem
  • Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study. (Prophylactic cranial irradiation will be possible for those participants with stable disease or better at the completion of the 4 cycles of chemotherapy with or without pembrolizumab.)
  • Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following:
  • Has completed treatment (eg, whole brain radiation treatment [WBRT], stereotactic radiosurgery, or equivalent) ≥14 days prior to the first dose of study treatment,
  • Has no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed ≥3 weeks after pre-treatment brain imaging, and
  • Is neurologically stable without the need for steroids for ≥7 days before first dose of study treatment.
  • Has had major surgery within 3 weeks prior to receiving the first dose of study treatment or has not recovered adequately from toxicity and/or complications from an intervention prior to receiving the first dose of study treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has a known history of interstitial lung disease
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has a known history of, or active, neurologic paraneoplastic syndrome
  • Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis
  • Has a history of a severe hypersensitivity reaction to treatment with another monoclonal antibody
  • Is taking chronic systemic steroids (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study treatment
  • Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Has received a live vaccine within 30 days 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-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 9 [TNFRSF9, OX-40, CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
  • Has severe hypersensitivity (Grade ≥3) to pembrolizumab and/or any of its excipients
  • Has an active infection requiring systemic therapy
  • 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 TB (Bacillus Tuberculosis)
  • Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
  • 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 through and up to 180 days after last dose of chemotherapeutic agents

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): NCT03066778


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

  Show 146 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03066778     History of Changes
Other Study ID Numbers: 3475-604
2016-004309-15 ( EudraCT Number )
173744 ( Registry Identifier: JAPIC-CTI )
MK-3475-604 ( Other Identifier: Merck Protocol Number )
First Posted: February 28, 2017    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018

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.:
Extensive stage small cell lung cancer (ES-SCLC)
Programmed cell death protein-1 (PD-1)
Programmed cell death-ligand 1 (PD-L1)
PD1
PDL1

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Etoposide phosphate
Cisplatin
Carboplatin
Etoposide
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action