Trial to evaluate the ability of afatinib to control disease in patients with advanced non-small cell lung cancer harbouring a specific gene mutation (change) in the human epidermal growth factor 2 (HER 2)

Phase 1

• Conditions: Advanced stage NSCLC, harbouring HER2 exon 20 mutations; MedDRA version: 18.0Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-005098-35-NL
• Lead Sponsor: ETOP (European Thoracic Oncology Platform)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06-19
• Last Update Posted: 22 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

- Histologically or cytologically confirmed, non-predominant squamous subtype, stage IIIB (non amenable to curative-intent multimodal treatment) or IV NSCLC, according to 7th TNM classification
- Tumour is platinum-refractory
- Measurable or evaluable disease (according to RECIST 1.1 criteria)
- Locally documented HER2 mutation
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Life expectancy >3 months
- Adequate haematological, renal and hepatic function
- Effective contraception, no pregnancy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

- Mixed small-cell and non-small-cell histologic features
- Uncontrolled lepto-meningeal metastatic disease
- Previous treatment with HER2 targeted antibody or tyrosine kinase inhibitor
- Any previous (in the past 3 years) or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast
- History or presence of clinically relevant cardiovascular abnormalities
- Other serious diseases or clinical conditions, including but not limited to uncontrolled active infection and any other serious underlying medical processes that could affect the patient’s capacity to participate in the trial
- Interstitial lung disease or pulmonary fibrosis
- Any concurrent systemic anticancer therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the ability of afatinib to control disease in pretreated patients with advanced NSCLC harbouring HER2 exon 20 mutations.;Secondary Objective: - To evaluate secondary measures of clinical efficacy including progression free survival (PFS), objective response rate (ORR) and overall survival (OS).<br>- To assess the safety and the tolerability of the treatment.;Primary end point(s): Disease control defined as complete or partial response, or disease stabilisation lasting at least 12 weeks.;Timepoint(s) of evaluation of this end point: Complete or partial response, or disease stabilisation lasting at least 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Progression-free survival by RECIST 1.1<br>- Objective response determined by RECIST 1.1<br>- Overall survival<br>- Adverse events graded according to CTCAE V4.0;Timepoint(s) of evaluation of this end point: - Progression-free survival:<br>Time from the date of enrolment until documented progression or<br>death, if progression is not documented. Censoring will occur at the last tumour assessment only if patient is lost to follow-up.<br>- Objective response:<br>Best overall response (CR or PR) across all assessment time-points during the period from enrolment to termination of trial treatment. Objective response to afatinib treatment will be determined using RECIST 1.1 criteria.<br>- Overall survival:<br>Time from the date of enrolment until death from any cause. Censoring will occur at the last follow-up date.<br>- Toxicity:<br>Adverse events classified according to NCI CTCAE version 4.