Afatinib in Previously Treated ESCC With EGFR Overexpression or EGFR Amplification (ESCC-A01)

• ClinicalTrials.gov Identifier: NCT03940976
• Recruitment Status: Unknown
• First Posted: May 7, 2019
• Last Update Posted: June 11, 2019
• Sponsor: Peking University
• Information provided by (Responsible Party): Shen Lin, Peking University

Study Description

Brief Summary:

This is a phase 2 trial investigating the effect and safety of afatinib 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	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Afatinib in Previously Treated Recurrent or Metastasic Esophageal Squamous Cell Carcinoma With EGFR Overexpression or EGFR Amplification (ESCC-A01)
• Actual Study Start Date: April 28, 2019
• Estimated Primary Completion Date: January 1, 2020
• Estimated Study Completion Date: May 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Afatinib	Drug: Afatinib; Afatinib is orally administered at 40mg Qd of each 28 day cycle.

Outcome Measures

Primary Outcome Measures :

1. Objective response rate [ Time Frame: 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 :

1. Incidence of Treatment-Related Adverse Events [ Time Frame: Until 30 days after the last treatment ]
   Number of adverse events of afatinib in patients with ESCC.
2. Disease control rate [ Time Frame: 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).
3. Progression free survival [ Time Frame: Up to 2 years ]
   Measure of time from study treatment to disease progression or death
4. Overall survival [ Time Frame: Up to 2 years ]
   Measure of time from study treatment to patient's death or lost to follow-up.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. Contraindications of afatinib.
2. Unable to take afatinib orally because of esophageal stenosis.
3. Currently receiving other effective regimens.
4. Previous anticipate other clinical trial within 4 weeks before entering this study.
5. No measurable lesions, eg. pleural fluid and ascites.
6. With other malignancy within 5 year, except non-melanoma skin cancer and cervical carcinoma in situ.
7. Heart failure or other sever organ dysfunction, eg. coronary artery disease, myocardial infarction within the last 6 months.
8. Mentally abnormal or disable cognition,including central nervous system (CNS) metastasis.
9. HIV infection, active hepatitis B or hepatitis C.
10. Unstable systemic diseases such as poorly controlled diabetes.
11. Interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease showed in X-ray/CT.
12. Keratitis, ulcerative keratitis or severe dry eye syndrome. Known hypersensitivity to study drug.
13. Pregnancy or lactation period.
14. Active severe infection within 14 days.

Contacts and Locations

Locations

China, Beijing

Peking University Cancer Hospital and Institute

Beijing, Beijing, China, 100142

Sponsors and Collaborators

Peking University

Investigators

• Principal Investigator: Lin Shen, Professor; Peking University Cancer Hospital and Institute

More Information

• Responsible Party: Shen Lin, Clinical Professor, Peking University
• ClinicalTrials.gov Identifier: NCT03940976
• Other Study ID Numbers: ESCC-A01
• First Posted: May 7, 2019
• Last Update Posted: June 11, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shen Lin, Peking University:

afatinib; EGFR Overexpression; EGFR Amplification

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Afatinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action