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

NCT ID: NCT03881111

Last Updated: 2020-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-21

Study Completion Date

2022-05-11

Brief Summary

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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.

Detailed Description

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

Conditions

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Esophageal Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Pembrolizumab + Cisplatin + 5-FU

Participants 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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

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

Cisplatin

Intervention Type DRUG

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-FU

Intervention Type DRUG

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.

Placebo + Cisplatin + 5-FU

Participants 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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Cisplatin

Intervention Type DRUG

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-FU

Intervention Type DRUG

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.

Interventions

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Pembrolizumab

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

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type DRUG

Cisplatin

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.

Intervention Type DRUG

5-FU

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.

Intervention Type DRUG

Other Intervention Names

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MK-3475

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Anhui Provincial Hospital ( Site 0106)

Hefei, Anhui, China

Site Status

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

Hefei, Anhui, China

Site Status

Peking Union Medical College Hospital ( Site 0123)

Beijing, Beijing Municipality, China

Site Status

The First Affiliated Hospital of Xiamen University ( Site 0119)

Xiamen, Fujian, China

Site Status

Guangdong General Hospital ( Site 0103)

Guangzhou, Guangdong, China

Site Status

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

Harbin, Heilongjiang, China

Site Status

Hunan Cancer Hospital ( Site 0105)

Changsha, Hunan, China

Site Status

PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)

Nanjing, Jiangsu, China

Site Status

Jiangsu Cancer Hospital ( Site 0117)

Nanjing, Jiangsu, China

Site Status

Zhongda Hospital Southeast University ( Site 0125)

Nanjing, Jiangsu, China

Site Status

Jilin Cancer Hospital ( Site 0101)

Changchun, Jilin, China

Site Status

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

Xi'an, Shannxi, China

Site Status

Zhejiang Cancer Hospital ( Site 0116)

Hangzhou, Zhejiang, China

Site Status

Beijing Cancer Hospital ( Site 0100)

Beijing, , China

Site Status

Fujian Provincial Cancer Hospital ( Site 0104)

Fuzhou, , China

Site Status

Shanghai Chest Hospital ( Site 0111)

Shanghai, , China

Site Status

Fudan University Shanghai Cancer Center ( Site 0108)

Shanghai, , China

Site Status

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

Shanghai, , China

Site Status

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

Wuhan, , China

Site Status

Henan Cancer Hospital ( Site 0107)

Zhengzhou, , China

Site Status

Countries

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China

Other Identifiers

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2017-000958-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

173739

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-590

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-590

Identifier Type: OTHER

Identifier Source: secondary_id

3475-590 China Extension

Identifier Type: -

Identifier Source: org_study_id

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