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

NCT ID: NCT03933449

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-29
• Study Completion Date: 2022-03-14

Brief 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 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.

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.

Conditions

Esophageal Carcinoma; Esophagogastric Junction Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab

Participants 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).

Group Type: EXPERIMENTAL

pembrolizumab

Intervention Type: BIOLOGICAL

IV infusion

Chemotherapy

Participants 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).

Group Type: ACTIVE_COMPARATOR

paclitaxel

Intervention Type: DRUG

IV infusion

docetaxel

Intervention Type: DRUG

IV infusion

irinotecan

Intervention Type: DRUG

IV infusion

Interventions

pembrolizumab

IV infusion

Intervention Type: BIOLOGICAL

paclitaxel

IV infusion

Intervention Type: DRUG

docetaxel

IV infusion

Intervention Type: DRUG

irinotecan

IV infusion

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA®; MK-3475; TAXOL®; TAXOTERE®; CAMPTOSAR®

Eligibility Criteria

Inclusion Criteria

• 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
• 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

Exclusion Criteria

• 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
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Anhui Provincial Hospital ( Site 0708)

Hefei, Anhui, China

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

Hefei, Anhui, China

Harbin Medical University Cancer Hospital ( Site 0714)

Harbin, Heilongjiang, China

Wuhan Tongji Hospital ( Site 0724)

Wuhan, Hubei, China

Hunan Cancer Hospital ( Site 0722)

Changsha, Hunan, China

Jiangsu Cancer Hospital (Site 0704)

Nanjing, Jiangsu, China

PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0706)

Nanjing, Jiangsu, China

Jilin Cancer Hospital ( Site 0718)

Changchun, Jilin, China

The First Hospital Of Jilin University ( Site 0719)

Changchun, Jilin, China

Zhejiang Cancer Hospital ( Site 0726)

Hangzhou, Zhejiang, China

Beijing Cancer Hospital ( Site 0700)

Beijing, , China

Chinese PLA General Hospital (Site 0703)

Beijing, , China

Peking Union Medical College Hospital ( Site 0712)

Beijing, , China

Fujian Medical University Union Hospital ( Site 0721)

Fuzhou, , China

Fujian Province Cancer Hospital ( ( Site 0717)

Fuzhou, , China

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

Hangzhou, , China

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

Hangzhou, , China

The Affiliated Hospital of Qingdao University ( Site 0709)

Qingdao, , China

Ruijin Hospital, Shanghai Jiaotong University ( Site 0701)

Shanghai, , China

Shanghai Chest Hospital ( Site 0727)

Shanghai, , China

Fudan University Shanghai Cancer Center ( Site 0723)

Shanghai, , China

Zhongshan Hospital affiliated to Fudan University ( Site 0715)

Shanghai, , China

Henan Cancer Hospital ( Site 0725)

Zhengzhou, , China

Countries

China

References

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.

Reference Type: RESULT

PMID: 34973513 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://merckoncologyclinicaltrials.com/

Merck Oncology Clinical Trial Information

Other Identifiers

163145

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3475-181

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-181

Identifier Type: OTHER

Identifier Source: secondary_id

3475-181 China Extension

Identifier Type: -

Identifier Source: org_study_id