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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01953913
• Other study ID #: 1200.66
• Status: Completed
• Phase: Phase 3
• Start date: September 30, 2013
• Est. completion date: July 6, 2018

Study information

• Verified date: June 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 542
• Est. completion date: July 6, 2018
• Est. primary completion date: July 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Afatinib
Patient will receive afatinib once daily

Locations

Country	Name	City	State
China	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	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai Chest Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin
India	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	Basavatarakam Indo - American Cancer Hospital & Research Ins	Hyderabad
India	Global Hospitals	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
Singapore	National Cancer Centre	Singapore
Taiwan	E-Da Hospital	Kaohsiung
Taiwan	NCKUH	Tainan
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Chang-Gung Memorial Hospital, Linkou	Taoyuan County

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

China,  Hong Kong,  India,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Serious Adverse Events (SAEs)	Percentage of participants with serious adverse events (SAEs).	From first drug administration up to 28 days after last drug administration, up to 1624 days.
Secondary	Time to Symptomatic Progression (TTSP)	Time to Symptomatic progression (TTSP) was defined as time from first administration of afatinib to date of first documented clinically significant symptomatic progression that required stopping the anti-cancer treatment according to investigator's assessment. 95% confidence intervals (CIs) for the median was calculated for TTSP using Greenwood' standard error estimate.	From first drug administration until date of first documented clinically significant symptomatic progression that required stopping afatinib treatment, up to 1624 days.
Secondary	Percentage of Participants With Drug-related (Afatinib-related) Adverse Events	Percentage of participants with drug-related (afatinib-related) adverse events.	From first drug administration up to 28 days after last drug administration, up to 1624 days.

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