Afatinib Plus Toripalimab in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification

Sponsor

Peking University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04880811

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Drug: Afatinib Drug: Toripalimab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

43 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 1, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Afatinib plus toripalimab	Drug: Afatinib Afatinib is orally administered at 40mg Qd of each 21 day cycle. Drug: Toripalimab Toripalimab is given by intravenous infusion at 200mg d1 of each 21 day cycle.

Arm

Intervention/Treatment

Experimental: Afatinib plus toripalimab

Drug: Afatinib

Afatinib is orally administered at 40mg Qd of each 21 day cycle.

Drug: Toripalimab

Toripalimab is given by intravenous infusion at 200mg d1 of each 21 day cycle.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Having signed informed consent.
Age 18 to 70 years old.
Histologically confirmed esophageal squamous carcinoma
Immunohistochemistry confirmed EGFR(3+) or EGFR-FISH-amplification or next generation sequencing confirmed EGFR-amplification.
Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed unresectable metastasic or recurrent ESCC.
Refractory or intolerant to at least one regimen.
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)
Life expectancy of ≥3 month
Eastern Cooperative Oncology Group (ECOG) 0-2
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)
No sever complication, such as active gastrointestinal bleeding, perforation, jaundice, obstruction, non-cancerous fever>38℃.
Good compliance

Exclusion Criteria:

Currently receiving other effective regimens.
Previous anticipate other clinical trial within 4 weeks before entering this study.
No measurable lesions, eg. pleural fluid and ascites.
With other malignancy within 5 year, except non-melanoma skin cancer and cervical carcinoma in situ.
Heart failure or other sever organ dysfunction, eg. coronary artery disease, myocardial infarction within the last 6 months.
Mentally abnormal or disable cognition,including central nervous system (CNS) metastasis.
HIV infection, active hepatitis B or hepatitis C.
Unstable systemic diseases such as poorly controlled diabetes.
Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease showed in X-ray/CT.
Keratitis, ulcerative keratitis or severe dry eye syndrome. Known hypersensitivity to study drug.
Pregnancy or lactation period.
Active severe infection within 14 days
Contraindications of afatinib.
Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding
Gastrointestinal perforation and/or fistula occurred within 3 months before enrollment
Patients with active autoimmune disease or stable disease with high risk of recurrence
Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment
Live vaccine was injected within 4 weeks before enrollment
Previously received treatment with EFFR-TKI