- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04807673
Pembrolizumab Plus Neoadjuvant Chemotherapy vs. Neoadjuvant Chemoradiotherapy for Locally Advanced ESCC (KEYSTONE-002) (KEYSTONE-002)
A Multicenter Randomized, Controlled Phase III Clinical Trial of Pembrolizumab Plus Paclitaxel and Cisplatin Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Locally Advanced Esophageal Squamous Cell Carcinoma (KEYSTONE-002)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Hongjing Jiang, MD,PhD
- Phone Number: 18622221069
- Email: jianghongjing@tmu.edu.cn
Study Contact Backup
- Name: xiaobin shang, MD,PhD
- Phone Number: 18622221071
- Email: shangxiaobin@tmu.edu.cn
Study Locations
-
-
Tianjin
-
Tianjin, Tianjin, China, 300060
- Recruiting
- Department of minimally invasive esophageal surgery, Tianjin Medical University Cancer Institute and Hospital
-
Contact:
- Hongjing Jiang, MD,PhD
- Phone Number: 18622221069
- Email: jianghongjing@tmu.edu.cn
-
Contact:
- xiaobin shang, MD,PhD
- Phone Number: 18622221071
- Email: shangxiaobin@tmu.edu.cn
-
Principal Investigator:
- Hongjing Jiang, MD,PhD
-
Principal Investigator:
- Yin Li, MD,PhD
-
Sub-Investigator:
- Zhigang Li, MD,PhD
-
Sub-Investigator:
- Hecheng Li, MD,PhD
-
Sub-Investigator:
- Peng Zhang, MD,PhD
-
Sub-Investigator:
- Ziqiang Tian, MD,PhD
-
Sub-Investigator:
- Jianqun Ma, MD,PhD
-
Sub-Investigator:
- Yegang MA, MD,PhD
-
Sub-Investigator:
- Shiping Guo, MD,PhD
-
Sub-Investigator:
- Haibo Cai, MD
-
Sub-Investigator:
- Hengxiao Lu, MD
-
Sub-Investigator:
- Lin Zhang, MD,PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed esophageal squamous cell carcinoma;
- R0 resectable thoracic esophageal cancer, cT1-3N1-2M0, cT2-3N0M0 (AJCC V8 TNM classification);
- No suspicious metastatic lymph nodes on the clavicle;
- Have a performance status of 0 or 1 on the ECOG Performance Scale;
- Age 18-75 years old, both men and women;
- Be willing and able to provide written informed consent/assent for the trial;
- Demonstrate adequate organ function ;
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required;
- Be willing to provide tissue, blood, and urine samples. Tissue should be from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly-obtained is defined as a specimen obtained up to 4 weeks (28 days) before initiation of treatment on Day 1.
- Have not received systemic or local treatment for esophageal cancer in the past.
Exclusion Criteria:
- Ineligibility or contraindication for esophagectomy;
- Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer
- Active autoimmune disease or history of autoimmune disease;
- Requiring systemic treatment with either corticosteroids or other immunosuppressive medications;
- Subjects with a history of symptomatic interstitial lung disease;
- History of allergy to study drug components;
- Women must not be pregnant or breast-feeding;
- Patient has received prior chemotherapy, radiotherapy, target therapy ,and immune therapy for this malignancy or any other past malignancy;
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pembrolizumab+ Paclitaxel+Cisplatin+ Surgery+Pembrolizumab (228)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W), paclitaxel 135mg/m^2 IV on Day 2 Q3W, and cisplatin 80 mg/m^2 IV on Day 2 Q3W, a total of three cycles. All treatments will be beginning on Day 1 of each 3-week dosing cycle. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. After surgery, pembrolizumab 200 mg IV on Day 1 Q3W lasting one year. Surgery: McKeown esophagectomy |
Neoadjuvant period: pembrolizumab 200mg IV D1, Q3W, and preoperative therapy with three cycles. Adjuvant period: pembrolizumab 200 mg IV D1, Q3W, up to one year, which should be performed within 3-6 weeks after surgery.
Other Names:
Neoadjuvant period: paclitaxel 135mg/m^2 IV on Day 2 Q3W, and a total of three cycles.
Neoadjuvant period: cisplatin 80 mg/m^2 IV on Day 2 Q3W, and a total of three cycles.
|
Experimental: neoadjuvant chemoradiotherapy+ Surgery (114)
neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23 fractions) with five cycles of TP(Paclitaxel 50mg/m^2 on D1 and Cisplatin 25mg/m^2 D1, repeated every week. Surgery should be done within 4-6 weeks after the last neoadjuvant treatment. Surgery: McKeown esophagectomy |
neoadjuvant chemoradiotherapy 41.4Gy(1.8Gy×23
fractions) with five cycles of TP(Paclitaxel 50mg/m^2 on D1 and Cisplatin 25mg/m^2 D1, repeated every week
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event Free Survival (EFS)
Time Frame: Up to approximately 2.5 years
|
EFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by investigator, or recurrence, or metastasis, or death due to any cause, whichever occurs first.
For this analysis, EFS will be assessed in participants with ESCC.
|
Up to approximately 2.5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic Complete Response (PCR)
Time Frame: 1 month after resection
|
PCR is defined as pT0N0M0
|
1 month after resection
|
Major pathologic response (MPR)
Time Frame: 1 month after resection
|
MPR is defined as viable tumor comprised ≤ 10% of resected tumor specimens.
|
1 month after resection
|
Disease Free Survival (DFS)
Time Frame: 3 and 5 years
|
Percentage of Participants With DFS, as Assessed by RECIST 1.1.
DFS is defined as the time from randomization to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.
|
3 and 5 years
|
Overall Survival (OS)
Time Frame: 3 and 5 years
|
OS is defined as the time from randomization to death due to any cause.
|
3 and 5 years
|
Objective response rate (ORR)
Time Frame: 1 month after resection
|
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 as assessed by investigator.
For this analysis, ORR will be assessed in all participants.
|
1 month after resection
|
assessment in perioperation
Time Frame: perioperative period
|
R0 resection rate, Time of operation, Quantity of bleeding, Thoracic Drainage, Days of Hospitalization, Rate of Operative Complication, Mortality of perioperation
|
perioperative period
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: up to 16 months
|
All participants with treatment-related adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Event,Version 4.0(CTC AE4.0).
|
up to 16 months
|
Quality of life differences (EORTC QLQ-C30)
Time Frame: 2.5 years
|
The quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-C30) questionnaire.
Patients will be invited to finish the questionnaire at the first day of randomization, before surgery and after surgery (3m, 6m, 12m and 24 months).
|
2.5 years
|
Quality of life differences (EORTC QLQ-OES18)
Time Frame: 2.5 years
|
The quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer patients (EORTC QLQ-OES18) questionnaire.
Patients will be invited to finish the questionnaire at the first day of randomization, before surgery and after surgery (3m, 6m, 12m and 24 months).
|
2.5 years
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Neoplasms, Squamous Cell
- Esophageal Neoplasms
- Carcinoma
- Carcinoma, Squamous Cell
- Esophageal Squamous Cell Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Paclitaxel
- Cisplatin
- Pembrolizumab
Other Study ID Numbers
- TianjinCIH20210096
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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