Clinical trial NCT01953913: Afatinib (BIBW 2992) in Advanced Non-Small Cell Lung Cancer Patients With EGFR Mutation
Official title: An Open Label, Multicentre, Single Arm Trial to Assess the Safety of Afatinib for Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring EGFR Mutation(s)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2013-10-01
Enrollment: 542
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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)

Primary outcomes:
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From first drug administration up to 28 days after last drug administration, up to 1624 days.
Secondary outcomes:
measure: Time to Symptomatic Progression (TTSP)
timeFrame: From first drug administration until date of first documented clinically significant symptomatic progression that required stopping afatinib treatment, up to 1624 days.
measure: Percentage of Participants With Drug-related (Afatinib-related) Adverse Events
timeFrame: From first drug administration up to 28 days after last drug administration, up to 1624 days.
Other outcomes:
Locations:
city: Beijing
country: China
facility: 307 Hospital of PLA
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Chinese PLA General Hospital
city: Changchun
country: China
facility: Jilin Province Cancer Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Linyi
country: China
facility: Lin Yi Tumor Hospital
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Bangalore
country: India
facility: Vikram Hospital
city: Bengaluru
country: India
facility: HCG Hospital
city: Calicut
country: India
facility: P VS Hospital Pvt Ltd
city: Chennai
country: India
facility: V S Hospital
city: Delhi
country: India
facility: Max Super Speciality Hospital, Delhi
city: Hyderabad
country: India
facility: Global Hospitals
city: Hyderabad
country: India
facility: Basavatarakam Indo - American Cancer Hospital & Research Ins
city: Jaipur
country: India
facility: SEAROC Cancer Centre
city: Kolkata,West Bengal
country: India
facility: B. P. Poddar Hospital & Medial Research Ltd
city: Madurai
country: India
facility: Asirvatham Multispeciality Hospital
city: Maharashtra
country: India
facility: Curie Manavata Cancer Centre
city: Maharashtra
country: India
facility: Shatabdi Superspeciality Hospital
city: Mumbai
country: India
facility: Prince Aly Khan Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Tainan
country: Taiwan
facility: NCKUH
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang-Gung Memorial Hospital, Linkou
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.