Esophageal Squamous Cell Carcinoma
Conditions
Keywords
afatinib, toripalimab, EGFR Overexpression, EGFR Amplification
Brief summary
This is a phase 2 trial investigating the effect and safety of afatinib plus toripalimab in previously treated recurrent or metastasic esophageal squamous cell carcinoma with EGFR overexpression or EGFR amplification.
Interventions
DRUGAfatinib
Afatinib is orally administered at 40mg Qd of each 21 day cycle.
DRUGToripalimab
Toripalimab is given by intravenous infusion at 200mg d1 of each 21 day cycle.
Sponsors
Peking University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Having signed informed consent. 2. Age 18 to 70 years old. 3. Histologically confirmed esophageal squamous carcinoma 4. Immunohistochemistry confirmed EGFR(3+) or EGFR-FISH-amplification or next generation sequencing confirmed EGFR-amplification. 5. Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed unresectable metastasic or recurrent ESCC. 6. Refractory or intolerant to at least one regimen. 7. Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria(diameter of the lesion should be more than 10mm by spiral CT or MRI, more than 20mm by common CT, the date of image should be less than 21 days before enrollment) 8. Life expectancy of ≥3 month 9. Eastern Cooperative Oncology Group (ECOG) 0-2 10. WBC\>3,000/mm3, absolute neutrophil count ≥1500/mm3, platelet\>100,000/mm3, Hb\>9g/dl，Bilirubin level \< 1.5 times ULN，Serum creatinine \<1.5 times ULN，ALT and AST\<2.5 times ULN ，AKP \< 2.5 times ULN ，(≤5 times ULN in patients with liver metastases)(within 7 days before enrollment) 11. No sever complication, such as active gastrointestinal bleeding, perforation, jaundice, obstruction, non-cancerous fever\>38℃. 12. Good compliance
Exclusion criteria
1. Currently receiving other effective regimens. 2. Previous anticipate other clinical trial within 4 weeks before entering this study. 3. No measurable lesions, eg. pleural fluid and ascites. 4. With other malignancy within 5 year, except non-melanoma skin cancer and cervical carcinoma in situ. 5. Heart failure or other sever organ dysfunction, eg. coronary artery disease, myocardial infarction within the last 6 months. 6. Mentally abnormal or disable cognition,including central nervous system (CNS) metastasis. 7. HIV infection, active hepatitis B or hepatitis C. 8. Unstable systemic diseases such as poorly controlled diabetes. 9. Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease showed in X-ray/CT. 10. Keratitis, ulcerative keratitis or severe dry eye syndrome. Known hypersensitivity to study drug. 11. Pregnancy or lactation period. 12. Active severe infection within 14 days 13. Contraindications of afatinib. 14. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding 15. Gastrointestinal perforation and/or fistula occurred within 3 months before enrollment 16. Patients with active autoimmune disease or stable disease with high risk of recurrence 17. Use corticosteroids (dose of prednisone or similar drugs\> 10mg/day) or other immunosuppressive agents within 14 days before enrollment 18. Live vaccine was injected within 4 weeks before enrollment 19. Previously received treatment with EFFR-TKI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months. | Percentage of patients who achieve partial response (PR) or complete response (CR) based on Response Evaluation Criteria In Solid Tumors (RECIST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | Up to 2 years | Measure of time from first response to disease progression or death |
| Disease control rate | From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months. | Percentage of patients who achieve partial response (PR) or complete response (CR) or stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST). |
| Incidence of Treatment-Related Adverse Events | Until 30 days after the last treatment | Number of adverse events. |
| Progression free survival | Up to 2 years | Measure of time from study treatment to disease progression or death. |
| Overall survival | Up to 2 years | Measure of time from study treatment to patient's death or lost to follow-up. |
Countries
China
Contacts
Primary ContactLin Shen, Professor
Backup ContactZhihao Lu, Professor
Outcome results
None listed