Afatinib (BIBW 2992) in Advanced Non-Small Cell Lung Cancer Patients With EGFR Mutation

NCT ID: NCT01953913

Last Updated: 2019-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 542 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2018-07-06

Brief Summary

Primary objective of the trial is to evaluate the safety of afatinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR (Epidermal growth factor receptor) mutation(s) and have never been treated with an EGFR-TKI (tyrosine kinase inhibitor). Secondary objective is to assess the time to symptomatic progression (as judged by investigator).

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Afatinib

Patient will receive afatinib once daily

Group Type: EXPERIMENTAL

Afatinib

Intervention Type: DRUG

Patient will receive afatinib once daily

Interventions

Afatinib

Patient will receive afatinib once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC)
• presence of Epidermal Growth Factor Receptor (EGFR) mutations in tumor biopsy
• male or female patients age 18 years or older (For India only, male or female patients age >=18 years and <=75 years)
• adequate organ function, defined as all of the following:

1. Absolute Neutrophil Count (ANC) > 1500/mm3. (ANC >1000/mm3 may be considered in special circumstances such as benign cyclical neutropenia as judged by the investigator and in discussion with the sponsor).

2. Platelet count >75,000/mm3

3. Serum creatinine < 1.5 times of the upper limit of normal

4. Total Bilirubin < 1.5 times upper limit of (institutional) normal (Patients with Gilbert's syndrome total bilirubin must be <4 times institutional upper limit of normal).

5. Aspartate Amino Transferase (AST) and Alanine Amino Transferase (ALT) < three times the upper limit of (institutional) normal (ULN) (if related to liver metastases < five times ULN). 5) Eastern Cooperative Oncology Group (ECOG) score between 0 - 2 6) written informed consent by patient or guardian prior to admission into the trial that is consistent with International Conference on Harmonisation (ICH)- Good Clinical Practice (GCP) guidelines and local law.

Exclusion Criteria

• prior treatment with an EGFR tyrosine kinase inhibitor (TKI)
• use of anti-cancer treatment within 2 weeks prior to start of trial treatment (continued use of anti-androgens and / or gonadorelin analogues for treatment of prostate cancer permitted)
• radiotherapy within 4 weeks prior to drug administration except as follows:

1. palliative radiation to organs other than chest may be allowed up to 2 weeks prior to drug administration, and

2. single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.

• major surgery within 4 weeks from day 1 of first dose of afatinib. At least 7 days should have elapsed since minor surgical procedure including placement of an access device or fine needle aspiration and at least 14 days for diagnostic or palliative video-assisted thoracoscopic surgery (VATS).
• known hypersensitivity to afatinib or any of its excipients
• history or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of >3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to starting trial treatment.
• Women of Child-Bearing Potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use medically acceptable method of contraception during the trial entry and for at least 4 weeks after treatment has ended. Adequate methods of contraception and Women of Child-Bearing Potential. Perimenopausal women must be amenorrhoeic for at least 24 months to be considered for non-childbearing potential.
• childbearing potential (see Section 4.2.3) who:

1. are nursing or

2. are pregnant or

3. are not using an acceptable method of birth control, or do not plan to continue using this method throughout the trial and/or do not agree to submit to pregnancy testing required by this protocol

• history of or co-existing condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the trial or interfere with the evaluation of safety for the trial drug
• previous or concomitant malignancies at other sites, except effectively treated nonmelanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
• requiring treatment with any of the prohibited concomitant medications listed, that cannot be stopped for the duration of trial participation
• known pre-existing interstitial lung disease
• presence of poorly controlled gastrointestinal disorders that could affect the absorption of the trial drug (e.g. Crohn's disease, ulcerative colitis, malabsorption, or CTC grade =2 diarrhoea of any aetiology) based on investigator assessment.
• Known active hepatitis B infection (defined as presence of Hepatitis B (HepB) sAg and/or HepB DNA), active Hepatitis C (HEP C) infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV) carrier.
• meningeal carcinomatosis
• symptomatic brain metastases (patients with brain metastases, who were previously treated, are eligible provided they have asymptomatic brain metastasis for at least 4 weeks on stable doses of medication)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

307 Hospital of PLA

Beijing, , China

Beijing Cancer Hospital

Beijing, , China

Chinese PLA General Hospital

Beijing, , China

Jilin Province Cancer Hospital

Changchun, , China

Guangdong Provincial People's Hospital

Guangzhou, , China

Zhejiang Cancer Hospital

Hangzhou, , China

Lin Yi Tumor Hospital

Linyi, , China

Jiangsu Cancer Hospital

Nanjing, , China

Shanghai Chest Hospital

Shanghai, , China

Fudan University Shanghai Cancer Center

Shanghai, , China

Shanghai Pulmonary Hospital

Shanghai, , China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, , China

Queen Mary Hospital

Hong Kong, , Hong Kong

Prince of Wales Hospital

Shatin, , Hong Kong

Vikram Hospital

Bangalore, , India

HCG Hospital

Bengaluru, , India

P VS Hospital Pvt Ltd

Calicut, , India

V S Hospital

Chennai, , India

Max Super Speciality Hospital, Delhi

Delhi, , India

Global Hospitals

Hyderabad, , India

Basavatarakam Indo - American Cancer Hospital & Research Ins

Hyderabad, , India

SEAROC Cancer Centre

Jaipur, , India

B. P. Poddar Hospital & Medial Research Ltd

Kolkata,West Bengal, , India

Asirvatham Multispeciality Hospital

Madurai, , India

Curie Manavata Cancer Centre

Maharashtra, , India

Shatabdi Superspeciality Hospital

Maharashtra, , India

Prince Aly Khan Hospital

Mumbai, , India

Ruby Hall Clinic

Pune, , India

National Cancer Centre

Singapore, , Singapore

E-Da Hospital

Kaohsiung City, , Taiwan

NCKUH

Tainan City, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Chang-Gung Memorial Hospital, Linkou

Taoyuan, , Taiwan

Countries

China; Hong Kong; India; Singapore; Taiwan

References

Zhao J, Bai H, Wang X, Wang Y, Duan J, Chen H, Xue Z, Tian Y, Cseh A, Huang DC, Wu YL, Wang J. Biomarker subset analysis of a phase IIIb, open-label study of afatinib in EGFR tyrosine kinase inhibitor-naive patients with EGFRm+ non-small-cell lung cancer. Future Oncol. 2022 Apr;18(12):1485-1497. doi: 10.2217/fon-2021-0394. Epub 2022 Feb 4.

Reference Type: DERIVED

PMID: 35114807 (View on PubMed)

Tu HY, Feng J, Shi M, Zhao J, Wang Y, Chang J, Wang J, Cheng Y, Zhu J, Tan EH, Li K, Zhang Y, Lee V, Yang CT, Su WC, Lam DC, Srinivasa BJ, Rajappa S, Ho CL, Lam KC, Hu Y, Bondarde SA, Liu X, Tian Y, Xue Z, Cseh A, Huang DC, Zhou C, Wu YL. A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naive Patients with EGFRm+ NSCLC: Final Analysis, with a Focus on Patients Enrolled at Sites in China. Target Oncol. 2022 Jan;17(1):1-13. doi: 10.1007/s11523-021-00859-6. Epub 2022 Jan 12.

Reference Type: DERIVED

PMID: 35020119 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

1200.66

Identifier Type: -

Identifier Source: org_study_id