Clinical trial NCT04880811: Afatinib Plus Toripalimab in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification
Official title: Phase 2 Study of Afatinib Plus Toripalimab in Previously Treated Recurrent or Metastasic Esophageal Squamous Cell Carcinoma With EGFR Overexpression or EGFR Amplification
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: afatinib
toripalimab
EGFR Overexpression
EGFR Amplification
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2021-05-11
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate
timeFrame: 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.
Secondary outcomes:
measure: Duration of response
timeFrame: Up to 2 years
measure: Disease control rate
timeFrame: 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.
measure: Incidence of Treatment-Related Adverse Events
timeFrame: Until 30 days after the last treatment
measure: Progression free survival
timeFrame: Up to 2 years
measure: Overall survival
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital and Institute
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, Professor
role: PRINCIPAL_INVESTIGATOR
References: