Clinical trial NCT02597946: Afatinib in NSCLC With HER2 Mutation
Official title: A Phase II Study of Afatinib in Patients With Advanced NSCLC Harboring HER2 Mutations, Previously Treated With Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2015-11-05
Enrollment: 18
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: to investigate effectiveness and safety of afatinib in the advanced NSCLC patients with HER2 mutations, previously treated with 1 or 2 chemotherapy regimens


Eligibility criteria: Inclusion criteria:

* Patients with Histologically or cytologically confirmed diagnosis of stage IIIb/IV NSCLC (AJCC 7.0), who had failed one or two systemic chemotherapy regimens, one of which must be platinum-based .
* Tumor tissue with HER2 mutations as confirmed by AmoyDx® HER2 Mutation Detection Kit
* Patients with at least one measurable tumor lesion that can accurately be measured by CT scan or MRI according to RECIST 1.1
* Age\>=18 years
* Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
* Adequate organ function
* Recovered from any previous therapy related toxicity to \<=Grade 1 at study entry (except for stable sensory neuropathy \<=Grade 2 and alopecia)
* Written informed consents that is consistent with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) and local GCP guidelines Inclusion criterion for Part B
* Adequate organ function, as inclusion criteria No.6
* ECOG performance score 0\~2
* More than 12 weeks clinical benefit (PR, Complete Response (CR), SD) in part A Further inclusion criteria apply

Exclusion criteria:

* Prior treatment with Epidermal Growth Factor Receptor (EGFR) or HER2 targeting small molecules or antibodies.
* Any chemo-, or immune anticancer therapy within 4 weeks prior to start of study treatment, Hormonal treatment within 2 weeks prior to start of study treatment, Radiotherapy within 4 weeks prior to start of treatment, except as follows:

  i.) Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to enter, and ii.) Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
* Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
* Known hypersensitivity to afatinib or the excipients of any of the trial drugs
* 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 randomisation.
* Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.
* Previous or concomitant malignancies at other sites, except effectively treated non-melanoma 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
* Known pre-existing interstitial lung disease.
* Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug.
* Active hepatitis B infection and/or active hepatitis C infection and/or known HIV carrier.
* Leptomeningeal carcinomatosis.
* Symptomatic brain metastases; To be eligible patients must be asymptomatic from brain metastases at least 4 weeks without requirement for steroids or anti-epileptic therapy.
* Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control for the duration of study participation and for at least 2 weeks after treatment has ended.
* Women who are pregnant, nursing, or who plan to become pregnant while in the trial Exclusion criterion for Part B Any known contraindication for paclitaxel treatment. Not able to tolerate lowest dose of afatinib. Peripheral polyneuropathy \>Grade 2 Further exclusion criteria apply

Primary outcomes:
measure: Percentage of Patients With Objective Response (OR) in Part A According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
timeFrame: CT Scan at Weeks 8 & 12 (for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment , ie., up to approximately 12 Months
Secondary outcomes:
measure: Percentage of Patients With Disease Control (DC) in Part A
timeFrame: CT Scan at Weeks 8 & 12(for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment, ie up to approximately 12 Months
measure: Progression Free Survival (PFS) in Part A
timeFrame: From the date of starting treatment of afatinib to the date of disease progression or to the date of death, ie up to approximately 12 Months
measure: Overall Survival (OS)
timeFrame: From start of treatment of afatinib until death from any cause, ie up to approximately 12 Months
measure: Time to Progression (TTP) in Part A
timeFrame: From the date of starting treatment of afatinib to the date of disease progression , ie up to approximately 12 Months
measure: Duration of Response (DOR) in Part A
timeFrame: CT Scan at Weeks 8 & 12(for week 12 tumor assessment, time window is +1week), then every 8 weeks thereafter, after week 52, assessments will be performed every 12 weeks until progression or start of further treatment, ie up to approximately 12 Months
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Province Tumor Hospital
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Nanchang
country: China
facility: The Second Affiliated Hospital to Nanchang University
city: Nanjing
country: China
facility: First Hospital Affiliated with Nanjing Medical University
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: