Clinical trial NCT03881111: First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)-China Extension 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Esophageal Neoplasms
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)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-03-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in all participants
timeFrame: Up to 2 years
measure: PFS per RECIST Version 1.1 in PD-L1 biomarker-positive participants
timeFrame: Up to 2 years
measure: Overall Survival (OS) in all participants
timeFrame: Up to 2 years
measure: OS in PD-L1 biomarker-positive participants
timeFrame: Up to 2 years
Secondary outcomes:
measure: Objective Response Rate (ORR) per RECIST 1.1 in all participants
timeFrame: Up to 2 years
measure: ORR per RECIST 1.1 in PD-L1 biomarker-positive participants
timeFrame: Up to 2 years
measure: Duration of Response (DOR) per RECIST 1.1 in all participants
timeFrame: Up to 2 years
measure: DOR per RECIST 1.1 in PD-L1 biomarker-positive participants
timeFrame: Up to 2 years
measure: Number of participants with an adverse event (AE)
timeFrame: Up to 27 months
measure: Number of participants discontinuing study treatment due to an AE
timeFrame: Up to 2 years
measure: Change from baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Score
timeFrame: Baseline, End of Treatment (~1 year)
measure: Change from baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Score
timeFrame: Baseline, End of Treatment (~1 year)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital ( Site 0106)
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University ( Site 0112)
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 0123)
state: Beijing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University ( Site 0119)
state: Fujian
city: Guangzhou
country: China
facility: Guangdong General Hospital ( Site 0103)
state: Guangdong
city: Harbin
country: China
facility: The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102)
state: Heilongjiang
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 0105)
state: Hunan
city: Nanjing
country: China
facility: PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital ( Site 0117)
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University ( Site 0125)
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital ( Site 0101)
state: Jilin
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120)
state: Shannxi
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 0116)
state: Zhejiang
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0100)
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital ( Site 0104)
city: Shanghai
country: China
facility: Shanghai Chest Hospital ( Site 0111)
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 0108)
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114)
city: Wuhan
country: China
facility: Tongji Medical College Huazhong University of Science and Technology ( Site 0109)
city: Zhengzhou
country: China
facility: Henan Cancer Hospital ( Site 0107)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: