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In this study, participants with esophageal squamous cell carcinoma will receive preoperative chemoradiotherapy with paclitaxel,carboplatin and pembrolizumab then undergo surgery. The primary study hypothesis is that adding pembrolizumab will increase complete pathologic response rate at surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| pembrolizumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-3475(pembrolizumab) | Drug | Neo-adjuvant chemoradiation period:The treatment consisted of taxol, carboplatin, pembrolizumab and radiation. The radiation treatment comprises 44.1Gy (2.1Gy/Fr, total 21Fr) and that will be about 5 weeks. Intensity modulated RT (IMRT) or 3D CRT (three-dimensional conformal radiotherapy) will be allowed. Surgery:Before surgery, abdomen/chest CT scan, endoscopic ultrasound (EUS), and gastroscopy with biopsy will be done. Surgery should be done within 12 weeks after last neo-adjuvant treatment. Adjuvant period:Adjuvant treatment with pembrolizumab 200mg every 2week (maximum 2 years) should be performed within 8 weeks after surgery (recommended period : 3-6 weeks after surgery). Gastroscopy and abdomen/chest CT scan will be performed at 6 month after surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Pathologic Response Rate | The primary endpoint of phase II study is to assess complete pathologic response rate. Definition of complete pathologic response is "no cancer cell, including lympho nodes" which corresponds with tumor regression score 0. Definition of pathologic response is as follows. Tumor regression score Grade 0 and 1 will be defined as "responder" and 2 and 3 will be considered as "non-responders" | Up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Free Survival | Disease free survival is defined from the time of surgery to initial replace or death. | Up to 3 years |
| Overall Survival | Overall survival is defined from the time of enrollment to death or last follow-up date. |
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Inclusion Criteria:
Histologically confirmed ESCC
Clinical stage T1N1-2 or T2-34aN0-12 (AJCC 7 TNM classification)
No evidence of metastasis
Be willing and able to provide written informed consent/assent for the trial.
Be 20 years of age on day of signing informed consent.
Be willing to provide tissue 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 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
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.
Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
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 treatment.
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.
Has a known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to pembrolizumab or any of its excipients.
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
Has another malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative surgery, or in situ cervical cancer.
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.
Has known history of, or any evidence of active, non-infectious pneumonitis.
Has an active infection requiring systemic therapy.
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.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
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.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has received a live vaccine within 30 days of planned start of study therapy.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yonsei Cancer Center, Yonsei University College of Medicine | Seoul | 03722 | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41449287 | Derived | Hong MH, Shin SK, Choi SJ, Ahn BC, Kim HR, Park SY, Kim DJ, Lee CG, Cho J, Kim JH, Kim HR, Kim YH, Lee GT, Park SR, Lee SK, Cho BC. Preoperative chemoradiotherapy plus pembrolizumab for esophageal squamous cell carcinoma (ACTS-29). Esophagus. 2026 Jan;23(1):99-110. doi: 10.1007/s10388-025-01165-0. Epub 2025 Dec 25. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Pembrolizumab | MK-3475(pembrolizumab): Neo-adjuvant chemoradiation period:The treatment consisted of taxol, carboplatin, pembrolizumab and radiation. The radiation treatment comprises 44.1Gy (2.1Gy/Fr, total 21Fr) and that will be about 5 weeks. Intensity modulated RT (IMRT) or 3D CRT (three-dimensional conformal radiotherapy) will be allowed. Surgery:Before surgery, abdomen/chest CT scan, endoscopic ultrasound (EUS), and gastroscopy with biopsy will be done. Surgery should be done within 12 weeks after last neo-adjuvant treatment. Adjuvant period:Adjuvant treatment with pembrolizumab 200mg every 2week (maximum 2 years) should be performed within 8 weeks after surgery (recommended period : 3-6 weeks after surgery). Gastroscopy and abdomen/chest CT scan will be performed at 6 month after surgery. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pembrolizumab | MK-3475(pembrolizumab): Neo-adjuvant chemoradiation period:The treatment consisted of taxol, carboplatin, pembrolizumab and radiation. The radiation treatment comprises 44.1Gy (2.1Gy/Fr, total 21Fr) and that will be about 5 weeks. Intensity modulated RT (IMRT) or 3D CRT (three-dimensional conformal radiotherapy) will be allowed. Surgery:Before surgery, abdomen/chest CT scan, endoscopic ultrasound (EUS), and gastroscopy with biopsy will be done. Surgery should be done within 12 weeks after last neo-adjuvant treatment. Adjuvant period:Adjuvant treatment with pembrolizumab 200mg every 2week (maximum 2 years) should be performed within 8 weeks after surgery (recommended period : 3-6 weeks after surgery). Gastroscopy and abdomen/chest CT scan will be performed at 6 month after surgery. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Complete Pathologic Response Rate | The primary endpoint of phase II study is to assess complete pathologic response rate. Definition of complete pathologic response is "no cancer cell, including lympho nodes" which corresponds with tumor regression score 0. Definition of pathologic response is as follows. Tumor regression score Grade 0 and 1 will be defined as "responder" and 2 and 3 will be considered as "non-responders" | Underwent surgery | Posted | Count of Participants | Participants | Up to 3 years |
|
During Neoadjuvant and Adjuvant Period (Up to 3.0 years) - Received neoadjuvant chemoradiotherapy with pembrolizumab - (Underwent surgery) Adjuvant pembrolizumab
according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pembrolizumab | MK-3475(pembrolizumab): Neo-adjuvant chemoradiation period:The treatment consisted of taxol, carboplatin, pembrolizumab and radiation. The radiation treatment comprises 44.1Gy (2.1Gy/Fr, total 21Fr) and that will be about 5 weeks. Intensity modulated RT (IMRT) or 3D CRT (three-dimensional conformal radiotherapy) will be allowed. Surgery:Before surgery, abdomen/chest CT scan, endoscopic ultrasound (EUS), and gastroscopy with biopsy will be done. Surgery should be done within 12 weeks after last neo-adjuvant treatment. Adjuvant period:Adjuvant treatment with pembrolizumab 200mg every 2week (maximum 2 years) should be performed within 8 weeks after surgery (recommended period : 3-6 weeks after surgery). Gastroscopy and abdomen/chest CT scan will be performed at 6 month after surgery. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Byoung Chul Cho | Yonsei University | +82 2 2228 4190 | cbc1971@yuhs.ac |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 27, 2018 | Apr 2, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000077277 | Esophageal Squamous Cell Carcinoma |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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|
| Up to 3 years |
| Pathologic Response Rate | Pathologic response rate is defined as tumor regression score. A score of '0' means 'No cancer cell, including lymph nodes'. A score of '1' means 'Single cells or small groups of cancer cells'. A score of '2' means 'Residual cancer cells outgrown by fibrosis'. A score of '3' means 'Minimum or no treatment effect'. | Up to 3 years |
| Safety According to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 | Grade 3-4 adverse events occurring during the neoadjuvant period (no death) | Up to 3 years |
| Event Free Survival | Event free survival is defined from the time of enrollment to 'event' included disease recurrence. | Up to 3 years |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
|
| Secondary | Disease Free Survival | Disease free survival is defined from the time of surgery to initial replace or death. | Underwent surgery | Posted | Median | 95% Confidence Interval | months | Up to 3 years |
|
|
|
| Secondary | Overall Survival | Overall survival is defined from the time of enrollment to death or last follow-up date. | Enrollment | Posted | Median | 95% Confidence Interval | months | Up to 3 years |
|
|
|
| Secondary | Pathologic Response Rate | Pathologic response rate is defined as tumor regression score. A score of '0' means 'No cancer cell, including lymph nodes'. A score of '1' means 'Single cells or small groups of cancer cells'. A score of '2' means 'Residual cancer cells outgrown by fibrosis'. A score of '3' means 'Minimum or no treatment effect'. | Underwent surgery | Posted | Number | participants | Up to 3 years |
|
|
|
| Secondary | Safety According to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 | Grade 3-4 adverse events occurring during the neoadjuvant period (no death) | Enrollment | Posted | Number | percentage of participants | Up to 3 years |
|
|
|
| Secondary | Event Free Survival | Event free survival is defined from the time of enrollment to 'event' included disease recurrence. | Enrollment | Posted | Median | 95% Confidence Interval | months | Up to 3 years |
|
|
|
| 1 |
| 28 |
| 10 |
| 28 |
| 28 |
| 28 |
| Fatigue | General disorders | Systematic Assessment |
|
| General weakness | Nervous system disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Esophagitis | Gastrointestinal disorders | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| General weakness | General disorders | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Weight loss | Investigations | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | Systematic Assessment |
|
| Rash acneiform | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hepatitis | Hepatobiliary disorders | Systematic Assessment |
|
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| D009369 | Neoplasms |
| D018307 | Neoplasms, Squamous Cell |
| D004938 | Esophageal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D006258 | Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| Title | Measurements |
|---|
|
| Score '3' |
|