AzTrials
AzTrials

Stomach NeoplasmsPhase 3NCT04859582

Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)-China Extension

A Phase 3 study testing Pembrolizumab, Cisplatin and 5-fluorouracil in people with Stomach Neoplasms, run by Merck Sharp & Dohme LLC at 28 sites in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in combination with chemotherapy (Cisplatin combined with 5-Fluorouracil [FP regimen] or oxaliplatin combined with capecitabine [CAPOX regimen]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stomach Neoplasms
What is being tested?
Pembrolizumab, Cisplatin and 5-fluorouracil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
28 sitesChina
Study dates
8 Nov 2018to 29 Nov 2024
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 gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status
  • Has human epidermal growth factor receptor 2 (HER2) negative cancer
  • Male participants must agree to use contraception during the intervention period and for at least 95 days after the last dose of chemotherapy, refrain from donating sperm and be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per study protocol unless confirmed to be azoospermic during this period
  • Female participants who are not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) OR is a WOCBP who agrees to use contraception or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for at least 180 days after the last dose of chemotherapy or for at least 120 days after the last dose of pembrolizumab, whichever is last, and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
  • Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator assessment
  • Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Show all 10Show fewer
  • Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis
  • Has provided tumor tissue sample for microsatellite instability (MSI) biomarker analysis
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the start of study intervention
  • Has adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment

Who cannot join

  • Has squamous cell or undifferentiated gastric cancer
  • Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, anticipation of the need for major surgery during the course of study intervention, or has not recovered adequately from the toxicity and/or complications from previous surgery
  • Has preexisting peripheral neuropathy >Grade 1
  • Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
  • Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant and/or adjuvant therapy as long as it was completed ≥6 months prior to randomization
  • Has received prior therapy with an anti-PD-1, anti-PD-L1 or anti- PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX- 40, CD137)
Show all 29Show fewer
  • Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization or has not recovered from all AEs due to any previous therapies to ≤Grade 1 or baseline
  • Has received prior radiotherapy within 2 weeks prior to study start or has not recovered from all previous radiation-related toxicities, required corticosteroids, and have not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to noncentral nervous system (CNS) disease
  • Has received a live or live-attenuated 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
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
  • Has known active CNS metastases and/or carcinomatous meningitis
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as Hepatitis C virus [HCV] ribonucleic acid [RNA] detected qualitatively) infection
  • Has a known history of active tuberculosis
  • Has hypokalemia (serum potassium less than the lower limit of normal)
  • Has hypomagnesemia (serum magnesium less than the lower limit of normal)
  • Has hypocalcemia (serum calcium less than the lower limit of normal)
  • Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is last
  • Has had an allogenic tissue/solid organ transplant
  • Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents (including, but not limited to, infusional 5-fluorouracil or oral capecitabine) and/or to any of their excipients
  • For participants taking cisplatin: has Grade ≥2 audiometric hearing loss

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

China28 sites

  • Cancer Hospital Chinese Academy of Medical Sciences ( Site 2421)

    Beijing, Beijing Municipality, 100021

  • Peking Union Medical College Hospital ( Site 2425)

    Beijing, Beijing Municipality, 100730

  • The First Hospital of Jilin University ( Site 2416)

    Changchun, Jilin, 130021

  • Xiangya Hospital Central-South University ( Site 2419)

    Changsha, Hunan, 410008

  • Hunan Cancer Hospital ( Site 2439)

    Changsha, Hunan, 410013

  • Changzhou Cancer Hospital-Changzhou Fourth Peoples Hospital ( Site 2441)

    Changzhou, Jiangsu, 213032

  • Fujian Medical University Union Hospital ( Site 2410)

    Fuzhou, Fujian, 350001

  • Fujian Provincial Cancer Hospital ( Site 2414)

    Fuzhou, Fujian, 350014

  • 900 Hospital of the Joint ( Site 2418)

    Fuzhou, Fujian, 350025

  • Guangdong General Hospital ( Site 2431)

    Guangzhou, Guangdong, 510080

  • Zhejiang Provincial People's Hospital ( Site 2446)

    Hangzhou, Zhejiang, 310014

  • Sir Run Run Show Hospital ( Site 2427)

    Hangzhou, Zhejiang, 310016

  • Zhejiang Cancer Hospital ( Site 2417)

    Hangzhou, Zhejiang, 310022

  • Harbin Medical University Cancer Hospital ( Site 2401)

    Harbin, Heilongjiang, 150081

  • The First Affiliated Hospital of Nanchang University ( Site 2440)

    Nanchang, Jiangxi, 330006

  • The 81st Hospital of PLA ( Site 2413)

    Nanjing, Jiangsu, 210002

  • Jiangsu Cancer Hospital ( Site 2432)

    Nanjing, Jiangsu, 210009

  • The Affiliated Hospital of Qingdao University ( Site 2405)

    Qingdao, Shandong, 266061

  • Shanghai East Hospital ( Site 2403)

    Shanghai, Shanghai Municipality, 200120

  • Zhongshan Hospital affiliated to Fudan University ( Site 2407)

    Shanghai, Shanghai Municipality, 210000

  • Peking University Shenzhen Hospital ( Site 2442)

    Shenzhen, Guangdong, 518036

  • Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2420)

    Ürümqi, Xinjiang, 830001

  • Hubei Cancer Hospital ( Site 2434)

    Wuhan, Hubei, 430079

  • The First Affiliated Hospital of Xiamen University ( Site 2430)

    Xiamen, Fujian, 361003

  • Zhongshan Hospital Xiamen University ( Site 2447)

    Xiamen, Fujian, 361004

  • 1st Affil hosp of Med College of Xi'an Jiaotong University ( Site 2428)

    XiAn, Shanxi, 710061

  • Yancheng First People s Hospital ( Site 2426)

    Yancheng, Jiangsu, 224000

  • Henan Cancer Hospital ( Site 2415)

    Zhengzhou, Henan, 450008

Other trials in China

About this study

Official title: A Phase 3, Randomized, Double-blind Clinical Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-line Treatment in Participants With HER2 Negative, Previously Untreated, Unresectable or Metastatic Gastric Orgastroesophageal Junction Adenocarcinoma (KEYNOTE-859)

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in combination with chemotherapy (Cisplatin combined with 5-Fluorouracil [FP regimen] or oxaliplatin combined with capecitabine [CAPOX regimen]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of human epidermal growth factor receptor 2 (HER2) negative advanced gastric or GEJ adenocarcinoma in adult Chinese participants.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS).

Read the detailed description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-859 (NCT03675737) plus those enrolled during the China extension enrollment period. A total of approximately 231 Chinese participants will be enrolled.

Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), programmed cell death ligand 2 (PD-L2, PDL2)
Medical subject headings
Stomach 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.

  • PembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

    Administered as an IV infusion on Day 1 Q3W

  • CisplatinDrug

    Also called PLATINOL®

    Administered as an IV infusion on Day 1 Q3W

  • 5-fluorouracilDrug

    Also called ADRUCIL®, 5FU

    Administered as a continuous IV infusion on Days 1-5 Q3W

  • OxaliplatinDrug

    Also called ELOXATIN®

    Administered as an IV infusion on Day 1 Q3W

  • CapecitabineDrug

    Also called XELODA®

    Administered orally BID on Days 1 to 14 Q3W

  • Placebo for PembrolizumabDrug

    Administered as an IV infusion on Day 1 Q3W

Study groups in NCT04859582
Study groupRoleWhat they receive
Pembrolizumab + FP or CAPOXExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m^2 IV on Day 1 Q3W + capecitabine 1000 mg/m^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Receives: Biological: Pembrolizumab; Drug: Cisplatin; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Capecitabine
Placebo + FP or CAPOXActive comparatorParticipants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m^2 IV on Day 1 Q3W and 5FU 800 mg/m^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m^2 IV on Day 1 Q3W + capecitabine 1000 mg/m^2 orally BID on Days 1 to 14 Q3W.
Receives: Drug: Cisplatin; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Placebo for Pembrolizumab

What is being measured

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

  1. Overall Survival (OS)

    OS is the time from randomization to death due to any cause.

    Measured: Up to approximately 65 months

Secondary outcomes (5)

  1. Progression-free Survival (PFS)

    PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).

    Measured: Up to approximately 65 months

  2. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants who have a confirmed 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, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR.

    Measured: Up to approximately 65 months

  3. Duration of Response (DOR)

    DOR is determined by disease assessment and is defined as the time from first response (CR or PR) to disease progression, or death from any cause, whichever occurs first.

    Measured: Up to approximately 65 months

  4. Percentage of Participants Experiencing Adverse Events (AEs)

    Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment.

    Measured: Up to approximately 65 months

  5. Percentage of Participants Discontinuing Study Drug Due to AEs

    Percentage of participants discontinuing study treatment due to an AE.

    Measured: Up to approximately 36 months

Timeline

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

  1. First posted26 Apr 2021
  2. Study start8 Nov 2018
  3. Primary completion29 Nov 2024 (estimated)
  4. Study completion29 Nov 2024 (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
NCT04859582
Sponsor's protocol ID
3475-859 China Extension
Other IDs
2018-001757-27, MK-3475-859 China Extension, KEYNOTE-859, 194649, 2018
Status last verified
Dec 2021
First submitted
23 Apr 2021
Last updated
16 Dec 2021
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-fluorouracil in people with Stomach Neoplasms, run by Merck Sharp & Dohme LLC at 28 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 10 inclusion and 29 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 16 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 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?

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?

Overall Survival (OS) (time frame: Up to approximately 65 months). 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 NCT04859582.

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 16 Dec 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in