Adjuvant Pembrolizumab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma at High Risk of Recurrence

NCT ID: NCT03322267

Last Updated: 2024-12-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-27

Study Completion Date

2025-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

In this study, participants with histologically diagnosed locally advanced esophageal squamous cell carcinoma who have received preoperative cisplatin-based chemoradiotherapy followed by surgery harbouring high risk of tumor recurrence will receive adjuvant cisplatin-based chemoradiotherapy followed by pembrolizumab. The primary study hypothesis is that adjuvant pembrolizumab will improve the 1-year recurrence-free survival rate compared to historical control.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

It is a single-arm phase II trial. The target population is patients with histologically diagnosed locally advanced ESCC patients (clinically staged at least T3 and/or any N and M0 by endoscopic ultrasonography \[EUS\] and fludeoxyglucose-positron emission tomography \[FDG-PET\]) who have received preoperative cisplatin-based chemoradiotherapy (CRT) followed by surgery, and exhibit high risk (closed or involved resection margin or extranodal invasion of involved lymph nodes or ypN2-3) of tumor recurrence. Eligible patients will receive adjuvant cisplatin-based CRT followed by pembrolizumab for 18 cycles.The study will enroll 46 patients in Taiwan. The estimated enrollment period is 2 years.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Esophageal Squamous Cell Carcinoma

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Adjuvant pembrolizumab Chemoradiotherapy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Adjuvant cisplatin-chemoradiotherapy followed by pembrolizumab
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Pembrolizumab

Adjuvant cisplatin-chemoradiotherapy followed by pembrolizumab

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type DRUG

Cisplatin (30 mg/m2, QW, 2 cycles) and radiotherapy (18-26 Gy/10-13 fractions) as adjuvant chemoradiotherapy, followed by pembrolizumab (200mg, Q3W, 18 cycles)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pembrolizumab

Cisplatin (30 mg/m2, QW, 2 cycles) and radiotherapy (18-26 Gy/10-13 fractions) as adjuvant chemoradiotherapy, followed by pembrolizumab (200mg, Q3W, 18 cycles)

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

cisplatin radiotherapy

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Be willing and able to provide written informed consent/assent for the trial.
2. Be ≥ 20 years of age on day of signing informed consent.
3. Be a diagnosed by pathology or cytology with a locally advanced ESCC, which is clinically stage according to the TNM system of the American Joint Committee on Cancer (AJCC) Cancer Staging System (7th edition), fulfilling one of the following criteria as determined by endoscopic ultrasound, computed tomography, bronchoscopy and positron emission tomography:

1. T3, N0, M0;
2. T4a, N0, M0;
3. T1-4a, N1-3, M0.
4. Have been treated with preoperative cisplatin-based CRT followed by esophagectomy with lymph node dissection for the locally advanced ESCC (defined by above criteria).
5. Have a performance status of 0 or 1 on the ECOG Performance Scale.
6. Exhibit at least one risk factor of tumor recurrence in the post-CRT surgical tissues:

1. Close (≤1mm) or involved margin;
2. Residual tumor cells in lymph nodes with extranodal invasion.
3. ypN2 or ypN3.
7. Adequate hemogram and organ function:

1. Absolute neutrophil count ≥1,500 /mcL; platelets ≥100,000 / mcL; hemoglobin ≥9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
2. Serum creatinine ≤1.5 X upper limit of normal or measured or calculated creatinine clearance ≥60 mL/min; serum total bilirubin ≤ 1.5 X ULN; AST and ALT ≤ 2.5 X ULN; albumin \>2.5 mg/dL; international normalized ratio or prothrombin time and activated partial thromboplastin time ≤1.5 X ULN unless subject is receiving anticoagulant therapy
8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to 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.
9. Female subjects of childbearing potential must be willing to use an adequate method of contraception. Contraception, for the course of the study through 120 days after the last dose of study medication.
10. Male subjects of childbearing potential must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria

1. Is diagnosed with adenocarcinoma of esophagus or gastroesophageal junction.
2. Has synchronously diagnosed with a squamous cell carcinoma of aero-digestive way, other than esophageal cancer.
3. Has prior malignancy, except for: (a) adequately treated basal cell or squamous cell skin cancer; (b) in-situ cervical cancer; (c) previously diagnosed malignancy which have been adequately treated and shown no evidence of recurrence for more than 5 years.
4. Is 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 treatment.
5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
6. Has a known history of active TB (Bacillus Tuberculosis)
7. Hypersensitivity to pembrolizumab or any of its excipients.
8. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
10. Has known history of, or any evidence of active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Hepatitis B virus positive subjects (defined as HBsAg positive and/or detectable HBV DNA).

* Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment.
* Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
18. Hepatitis C virus positive subjects (defined as anti-HCV Ab positive and detectable HCV RNA).

* Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
* Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
19. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and active Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
20. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
21. Has received organ transplantation.
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

National Taiwan University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Chih-Hung Hsu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Taiwan

References

Explore related publications, articles, or registry entries linked to this study.

Guo JC, Huang TC, Kuo HY, Lin CC, Hsu FM, Cheng JC, Huang YL, Hsieh MS, Huang PM, Lee JM, Wu SL, Hsu CH. Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study. Cancer Immunol Immunother. 2024 Sep 9;73(11):230. doi: 10.1007/s00262-024-03826-y.

Reference Type DERIVED
PMID: 39249605 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

201708042MIPD

Identifier Type: -

Identifier Source: org_study_id