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Esophageal NeoplasmsPhase 3NCT03881111

First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)-China Extension Study

A Phase 3 study testing Pembrolizumab, Cisplatin and 5-FU in people with Esophageal Neoplasms, run by Merck Sharp & Dohme LLC at 20 sites in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this Chinese extension study is to evaluate efficacy and safety of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) chemotherapy versus placebo plus cisplatin and 5-FU chemotherapy as first-line treatment in a Chinese cohort of participants with locally advanced or metastatic esophageal carcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Neoplasms
What is being tested?
Pembrolizumab, Cisplatin and 5-FU
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
20 sitesChina
Study dates
21 Jan 2019to 11 May 2022
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ)
  • Has measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment
  • Eastern Cooperative Group (ECOG) performance status of 0 to 1
  • Can provide either a newly obtained or archival tissue sample for PD-L1 by immunohistochemistry analysis
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization and be willing to use an adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with spermicide, etc.) for the course of the study through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin
  • Male participants of childbearing potential must agree to use an adequate method of contraception (e.g. abstinence, vasectomy, male condom, etc.) 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 cisplatin, and refrain from donating sperm during this period
  • Has adequate organ function

Who cannot join

  • Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)
  • Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
  • Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
  • 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, in situ breast cancer that has undergone potentially curative therapy, and in situ or intramucosal pharyngeal cancer
  • Has known active central nervous system metastases and/or carcinomatous meningitis.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
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  • 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 to the first dose of study treatment, or has a history of organ transplant, including allogeneic stem cell transplant
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis, or has an active infection requiring systemic therapy
  • 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 medication and up to 180 days after last dose of cisplatin
  • Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical trial
  • Has severe hypersensitivity (≥ Grade 3) to any study treatment (pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients
  • Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human immunodeficiency virus (HIV) infection
  • Has known history of or is positive for hepatitis B or hepatitis C
  • Has received a live vaccine within 30 days prior to the first dose of study treatment
  • Has had radiotherapy within 14 days of randomization. Participants who received radiotherapy >14 days prior to randomization must have completely recovered from any radiotherapy-related AEs/toxicities

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

China20 sites

  • Peking Union Medical College Hospital ( Site 0123)

    Beijing, Beijing Municipality, 100032

  • Beijing Cancer Hospital ( Site 0100)

    Beijing, 100142

  • Jilin Cancer Hospital ( Site 0101)

    Changchun, Jilin, 130012

  • Hunan Cancer Hospital ( Site 0105)

    Changsha, Hunan, 410013

  • Fujian Provincial Cancer Hospital ( Site 0104)

    Fuzhou, 350014

  • Guangdong General Hospital ( Site 0103)

    Guangzhou, Guangdong, 510120

  • Zhejiang Cancer Hospital ( Site 0116)

    Hangzhou, Zhejiang, 310022

  • The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102)

    Harbin, Heilongjiang, 150081

  • Anhui Provincial Hospital ( Site 0106)

    Hefei, Anhui, 230036

  • The First Affiliated Hospital of Anhui Medical University ( Site 0112)

    Hefei, Anhui, 230088

  • PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)

    Nanjing, Jiangsu, 210002

  • Jiangsu Cancer Hospital ( Site 0117)

    Nanjing, Jiangsu, 210009

  • Zhongda Hospital Southeast University ( Site 0125)

    Nanjing, Jiangsu, 210009

  • Shanghai Chest Hospital ( Site 0111)

    Shanghai, 200030

  • Fudan University Shanghai Cancer Center ( Site 0108)

    Shanghai, 200032

  • Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114)

    Shanghai, 200127

  • Tongji Medical College Huazhong University of Science and Technology ( Site 0109)

    Wuhan, 430030

  • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120)

    Xi'an, Shannxi, 710061

  • The First Affiliated Hospital of Xiamen University ( Site 0119)

    Xiamen, Fujian, 361000

  • Henan Cancer Hospital ( Site 0107)

    Zhengzhou, 450008

Other trials in China

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Pembrolizumab (MK-3475) in Combination With Cisplatin and 5-Fluorouracil Versus Placebo in Combination With Cisplatin and 5-Fluorouracil as First-Line Treatment in Subjects With Advanced/Metastatic Esophageal Carcinoma (KEYNOTE-590)

The purpose of this Chinese extension study is to evaluate efficacy and safety of pembrolizumab plus cisplatin and 5-fluorouracil (5-FU) chemotherapy versus placebo plus cisplatin and 5-FU chemotherapy as first-line treatment in a Chinese cohort of participants with locally advanced or metastatic esophageal carcinoma.

The primary efficacy hypotheses are that both progression-free survival (PFS), according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and determined by blinded independent central review, and overall survival (OS) are superior with pembrolizumab plus chemotherapy compared with placebo plus chemotherapy in all Chinese participants as well as Chinese participants whose tumors are programmed cell death-ligand 1 (PD-L1)-positive.

Read the detailed description

The Chinese extension to MK-3475-590 (NCT03189719) will enroll a total of approximately 90 participants.

Being tested
Pembrolizumab, Placebo, Cisplatin, 5-FU
Keywords
Programmed Cell Death-1 (PD-1), Programmed Cell Death 1 (PD1), Programmed Cell Death-Ligand 1 (PD-L1, PDL1), Programmed Cell Death-Ligand 2 (PD-L2, PDL2)
Medical subject headings
Esophageal Neoplasms

What participants receive

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

  • PembrolizumabBiological

    Also called MK-3475

    200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.

  • PlaceboDrug

    Placebo to pembrolizumab (saline) administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.

  • CisplatinDrug

    80 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle. Duration of cisplatin treatment will be capped at 6 doses.

  • 5-FUDrug

    800 mg/m^2/day (4000 mg/m^2 total per cycle) administered as continuous IV infusion on Days 1 to 5 (120 hours) of each 3-week cycle, or per local standard for 5-FU administration.

Study groups in NCT03881111
Study groupRoleWhat they receive
Pembrolizumab + Cisplatin + 5-FUExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W), cisplatin 80 mg/m^2 IV Q3W, and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours). All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Receives: Biological: Pembrolizumab; Drug: Cisplatin; Drug: 5-FU
Placebo + Cisplatin + 5-FUPlacebo comparatorParticipants receive placebo to pembrolizumab (saline) IV Q3W, cisplatin 80 mg/m^2 IV Q3W, and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours). All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.
Receives: Drug: Placebo; Drug: Cisplatin; Drug: 5-FU

What is being measured

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

  1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in all participants

    PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. For this analysis, PFS will be assessed in all participants.

    Measured: Up to 2 years

  2. PFS per RECIST Version 1.1 in PD-L1 biomarker-positive participants

    PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first. For this analysis, PFS will be assessed in PD-L1 biomarker-positive participants.

    Measured: Up to 2 years

  3. Overall Survival (OS) in all participants

    OS is defined as the time from randomization to death due to any cause. For this analysis, OS will be assessed in all participants.

    Measured: Up to 2 years

  4. OS in PD-L1 biomarker-positive participants

    OS is defined as the time from randomization to death due to any cause. For this analysis, OS will be assessed in PD-L1 biomarker-positive participants.

    Measured: Up to 2 years

Secondary outcomes (8)

  1. Objective Response Rate (ORR) per RECIST 1.1 in all participants

    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. For this analysis, ORR will be assessed in all participants.

    Measured: Up to 2 years

  2. ORR per RECIST 1.1 in PD-L1 biomarker-positive participants

    ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. For this analysis, ORR will be assessed in PD-L1 biomarker-positive participants.

    Measured: Up to 2 years

  3. Duration of Response (DOR) per RECIST 1.1 in all participants

    For participants who demonstrate CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 based on assessments by blinded independent central review or death due to any cause, whichever occurs first. For this analysis, DOR will be assessed in all participants.

    Measured: Up to 2 years

  4. DOR per RECIST 1.1 in PD-L1 biomarker-positive participants

    For participants who demonstrate CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), DOR is defined as the time from first documented evidence of CR or PR until disease progression per RECIST 1.1 based on assessments by blinded independent central review or death due to any cause, whichever occurs first. For this analysis, DOR will be assessed in PD-L1 biomarker-positive participants.

    Measured: Up to 2 years

  5. Number of participants with an adverse event (AE)

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

    Measured: Up to 27 months

  6. Number of participants discontinuing study treatment due to an AE

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

    Measured: Up to 2 years

  7. Change from baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Score

    The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer. It contains 30 questions (items), 24 of which aggregate into nine multi-item scales representing various aspects, or dimensions, of quality of life (QOL): one global scale, five functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea, pain), and six additional single-symptom items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Individual items are scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation; a higher score on the global and functional scales represents a higher ("better") level of functioning, and a higher score on the symptom scale represents a higher ("worse") level of symptoms.

    Measured: Baseline, End of Treatment (~1 year)

  8. Change from baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Score

    The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer. It contains 18 items and is based on four subscales-dysphagia (three items), eating (four items), reflux (two items) and pain (three items), as well as six single-item subscales-saliva swallowing, choking, dry mouth, taste, cough and speech. All items are scored using a four-point Likert scale that offers these response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores are standardized into a range of 0 to 100 by linear transformation; higher symptom scores represent a higher ("worse") level of symptoms.

    Measured: Baseline, End of Treatment (~1 year)

Timeline

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

  1. First posted19 Mar 2019
  2. Study start21 Jan 2019
  3. Primary completion11 May 2021 (estimated)
  4. Study completion11 May 2022 (estimated)

Why it stopped: Withdrawn due to protocol amendment

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
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03881111
Sponsor's protocol ID
3475-590 China Extension
Other IDs
2017-000958-19, 173739, MK-3475-590, KEYNOTE-590, 2017
Status last verified
Feb 2020
First submitted
18 Mar 2019
Last updated
11 Feb 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Cisplatin and 5-FU in people with Esophageal Neoplasms, run by Merck Sharp & Dohme LLC at 20 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 7 inclusion and 15 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: withdrawn, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 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. Some participants in this study may receive a placebo. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in all participants (time frame: Up to 2 years). The study lists 4 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 NCT03881111.

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 11 Feb 2020.

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