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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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This study is to evaluate the effectiveness of treatment for esophagogastric junction carcinoma, total neoadjuvant therapy (TNT) including pembrolizumab and FLOT is conducted, aiming to choose between surgery or organ preservation treatment strategies.
In Immunochemotherapy before short-term radiation therapy, pembrolizumab 200mg will be intravenously infused at 21-day intervals for 2 doses. FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200mg/m2, 5-FU 2600 mg/m2) will be intravenously infused at 14-day intervals for 2 doses.
Regarding short-term radiotherapy, irradiation will be delivered from day1 to day5, with a dose of 5 Gy per fraction for a total of 25 Gy.
In Immunochemotherapy after short-term radiation therapy, pembrolizumab 200mg will be intravenously infused on day 8. FLOT will be intravenously infused on day 1 and day15.
If CR or Near CR is achieved after the first and second efficacy assessment, pembrolizumab 200mg will be intravenously infused at 21-day intervals for 14 doses and FLOT will be intravenously infused at 14-day intervals for 4 doses as immunochemotherapy as non-operative management (NOM).
If CR or Near CR is not achieved after the first or second efficacy assessment, surgery will be performed. And then pembrolizumab 200mg will be intravenously infused at 21-day intervals for 14 doses and FLOT will be intravenously infused at 14-day intervals for 4 doses as Postoperative adjuvant immunochemotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pembrolizumab plus FLOT, Ratiation | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pembrolizumab | Drug | Pembrolizumab 200mg will be administered via intravenous infusion over 30 minutes, twice at 21-day intervals. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 3-year event-free survival (EFS) rate | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Organ-sparing survival | 3 years | |
| Overall survival (OS) | 3 years | |
| Clinical response rate |
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<Inclusion Criteria>
[1] Neutrophil count ≥1,500/mm3 [2] Hemoglobin ≥9.0 g/dL [3] Platelet counts ≥100,000/mm3 [4] Total bilirubin ≤1.5 mg/dL [5] AST (GOT) ≤100 IU/L [6] ALT (GPT) ≤100 IU/L [7] Serum creatinine ≤1.5 mg/dL 6) Patients who did not receive blood transfusion within 7 days before registration (ineligible if transfusion was performed on the same day of the week one week before the date of registration).
7)Female patients of childbearing potential who tested negative for pregnancy within 14 days before registration. Male and female patients who have agreed to practice appropriate highly effective contraception with low user dependency during the study and for up to 120 days after discontinuation of the investigational drug.
8)Patients who have given consent to provide samples for biomarker analysis. 9)Patients who have given their own written consent to participate in the study
<Exclusion Criteria>
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kohei Shitara, MD | Contact | +81-4-7133-1111 | 91520 | pemflot-tnt@east.ncc.go.jp |
| Izuma Nakayama, MD | Contact | +81-4-7133-1111 | 92339 | pemflot-tnt@east.ncc.go.jp |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Center Hospital East | Recruiting | Kashiwa | Chiba | 277 | Japan |
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| Docetaxel | Drug | Docetaxel 50 mg/m2 will be administered over 60 minutes. |
|
| Oxaliplatin | Drug | Oxaliplatin 85 mg/m2 will be administered over 2 hours. |
|
| Levofolinate | Drug | Leucovorin 200 mg/m2 will be administered over 2 hours. |
|
| Fluorouracil (5-FU) | Drug | 5-FU 2600 mg/m2 will be administered over 24 hours. |
|
| Radiation Therapy | Radiation | 25Gy (5Gy×5fr) |
|
| 3 years |
| Clinical complete response rate | 3 years |
| Major pathological response rate (MPR rate) | 3 years |
| Pathological complete response rate (pCR rate) | 3 years |
| R0 resection rate (R0 rate) | 3 years |
| TNT completion rate | 3 years |
| Treatment completion rate | 3 years |
| Adverse event incidence rate | 3 years |
| Post-treatment ctDNA clearance | 3 years |
| EORTC QLQ-C30 | We are reporting scores from the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30). The scores were transformed to a 0-100 scale following the official EORTC scoring manual. For functional scales and global health status, higher scores indicate a better outcome. For symptom scales/items, higher scores indicate a worse outcome. | 3 years |
| EORTC QLQ-OG25 | We are reporting scores from the EORTC QLQ-OG25 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophago-Gastric module). The scores were transformed to a 0-100 scale following the official EORTC scoring manual. All scales and single items in the QLQ-OG25 are symptom-based. Therefore, higher scores indicate worse symptoms or poorer quality of life. | 3 years |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D000077143 | Docetaxel |
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D056831 | Coordination Complexes |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013812 | Therapeutics |
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