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Esophageal CarcinomaPhase 3NCT03933449

Study of Pembrolizumab (MK-3475) Versus Investigator's Choice of Chemotherapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)-China Extension Study

A Phase 3 study testing pembrolizumab, paclitaxel and docetaxel in people with Esophageal Carcinoma and Esophagogastric Junction Carcinoma, run by Merck Sharp & Dohme LLC at 23 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

In the China extension study, Chinese participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that has progressed after first-line standard therapy will be randomized to receive either single agent… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pembrolizumab, paclitaxel and docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
123 participants
Where
23 sitesChina
Study dates
29 Dec 2016to 14 Mar 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ
  • Metastatic disease or locally advanced, unresectable disease
  • Life expectancy of greater than 3 months
  • Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
  • Documented radiographic or clinical disease progression on no more or less than one previous line of standard therapy
Show all 9Show fewer
  • Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral immune-related testing and for anti-programmed cell death (PD)-1
  • Participants of reproductive potential must be willing to use adequate contraception for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
  • Adequate organ function

Who cannot join

  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study medication
  • Active autoimmune disease that has required systemic treatment in past 2 years
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
  • Known central nervous system (CNS) metastases and/or carcinomatous meningitis (includes past history or current metastasis)
  • Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
  • Has had a severe hypersensitivity reaction to treatment with another mAb
Show all 19Show fewer
  • Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) study
  • Has a known additional malignancy that has progressed or required active treatment within the last 5 years with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers, and in-situ or intra-mucosal pharyngeal cancer
  • Received a live vaccine within 30 days of the first dose of study medication
  • Known history of Human Immunodeficiency Virus (HIV) infection
  • Known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or known active hepatitis C [hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody is detected]
  • History of non-infectious pneumonitis that required steroids or current pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Pregnant, 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 pembrolizumab or through 180 days after the last dose of paclitaxel, docetaxel or irinotecan
  • Known allergy, hypersensitivity, or contraindication to paclitaxel, docetaxel, or irinotecan or any components used in their preparation
  • Experienced weight loss > 10% over ~2 months prior to first dose of study therapy
  • Has ascites or pleural effusion by physical exam
  • Has experienced documented objective radiographic or clinical disease progression during or after receiving more than 1 line of therapy.

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

China23 sites

  • Beijing Cancer Hospital ( Site 0700)

    Beijing, 100042

  • Chinese PLA General Hospital (Site 0703)

    Beijing, 100042

  • Peking Union Medical College Hospital ( Site 0712)

    Beijing, 100730

  • Jilin Cancer Hospital ( Site 0718)

    Changchun, Jilin, 130012

  • The First Hospital Of Jilin University ( Site 0719)

    Changchun, Jilin, 130021

  • Hunan Cancer Hospital ( Site 0722)

    Changsha, Hunan, 410013

  • Fujian Medical University Union Hospital ( Site 0721)

    Fuzhou, 350001

  • Fujian Province Cancer Hospital ( ( Site 0717)

    Fuzhou, 350014

  • Zhejiang Cancer Hospital ( Site 0726)

    Hangzhou, Zhejiang, 310022

  • The Second Affiliated Hospital of Zhejiang University School of Medicine ( Site 0705)

    Hangzhou, 310009

  • Sir Sun Sun Shaw Hosp, Zhejiang Univ,Oncology dept. ( Site 0720)

    Hangzhou, 310016

  • Harbin Medical University Cancer Hospital ( Site 0714)

    Harbin, Heilongjiang, 150081

  • Anhui Provincial Hospital ( Site 0708)

    Hefei, Anhui, 230001

  • The First Affiliated Hospital of Anhui Medical University ( Site 0707)

    Hefei, Anhui, 230022

  • Jiangsu Cancer Hospital (Site 0704)

    Nanjing, Jiangsu, 210000

  • PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0706)

    Nanjing, Jiangsu, 210002

  • The Affiliated Hospital of Qingdao University ( Site 0709)

    Qingdao, 266003

  • Ruijin Hospital, Shanghai Jiaotong University ( Site 0701)

    Shanghai, 200025

  • Shanghai Chest Hospital ( Site 0727)

    Shanghai, 200030

  • Fudan University Shanghai Cancer Center ( Site 0723)

    Shanghai, 200032

  • Zhongshan Hospital affiliated to Fudan University ( Site 0715)

    Shanghai, 200032

  • Wuhan Tongji Hospital ( Site 0724)

    Wuhan, Hubei, 430030

  • Henan Cancer Hospital ( Site 0725)

    Zhengzhou, 450008

Other trials in China

About this study

Official title: A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Progressed After First-Line Standard Therapy (KEYNOTE-181)

In the China extension study, Chinese participants with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the esophagogastric junction (EGJ) that has progressed after first-line standard therapy will be randomized to receive either single agent pembrolizumab or the Investigator's choice of chemotherapy with paclitaxel, docetaxel, or irinotecan.

The primary extension study hypothesis is that treatment with pembrolizumab will prolong overall survival (OS) as compared to treatment with chemotherapy.

Read the detailed description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-181 (NCT02564263) plus those enrolled during the China extension enrollment period.

Per protocol, response/progression or adverse events during the second pembrolizumab course will not be counted towards efficacy outcome measures or safety outcome measures.

Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Death-Ligand 2 (PDL2, PD-L2), Gene expression profiling (GEP)
Medical subject headings
Esophageal Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03933449
Study groupRoleWhat they receive
PembrolizumabExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to ~2 years). Participants who complete the first course of up to 35 administrations of pembrolizumab (~2 years) but progress after discontinuation, may be eligible for a second course of pembrolizumab at the investigator's discretion, at the same dose and schedule at 200 mg IV on Day 1 of each 3-week cycle for up to 17 cycles (up to ~1 year).
Receives: Biological: pembrolizumab
ChemotherapyActive comparatorParticipants receive Investigator's choice of chemotherapy: paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to ~2 years).
Receives: Drug: paclitaxel; Drug: docetaxel; Drug: irinotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS) in All Participants

    OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in all participants is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  2. Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

    OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with a PD-L1 CPS ≥10 is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  3. Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

    OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with SCC of the esophagus is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

Secondary outcomes (8)

  1. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants

    ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of all participants who experienced a CR or PR for the first pembrolizumab course is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  2. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

    ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR for the first pembrolizumab course is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  3. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

    ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with SCC of the esophagus who experienced a CR or PR for the first pembrolizumab course is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  4. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 in all participants is presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  5. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  6. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

    PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with SCC of the esophagus.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  7. Number of Participants Experiencing an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced ≥1 AE for the first pembrolizumab course are presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

  8. Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE for the first pembrolizumab course are presented.

    Measured: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2019
  2. Study start29 Dec 2016
  3. Primary completion13 Feb 2019
  4. Study completion14 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
123 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03933449
Sponsor's protocol ID
3475-181 China Extension
Other IDs
163145, MK-3475-181, KEYNOTE-181
Status last verified
Mar 2023
First submitted
29 Apr 2019
Last updated
29 Mar 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Cao Y, Qin S, Luo S, Li Z, Cheng Y, Fan Y, Sun Y, Yin X, Yuan X, Li W, Liu T, Hsu CH, Lin X, Kim SB, Kojima T, Zhang J, Lee SH, Bai Y, Muro K, Doi T, Bai C, Gu K, Pan HM, Bai L, Yang JW, Cui Y, Lu W, Chen J. Pembrolizumab versus chemotherapy for patients with esophageal squamous cell carcinoma enrolled in the randomized KEYNOTE-181 trial in Asia. ESMO Open. 2022 Feb;7(1):100341. doi: 10.1016/j.esmoop.2021.100341. Epub 2021 Dec 29.

    PubMed 34973513

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing pembrolizumab, paclitaxel and docetaxel in people with Esophageal Carcinoma and Esophagogastric Junction Carcinoma, run by Merck Sharp & Dohme LLC at 23 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) in All Participants (time frame: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03933449, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.

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