Biomarker Study Accompanying the AIO-TRK-0114 Study (MARBLE)

Study Overview
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Brief Summary
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To compare the efficacy of afatinib maintenance with pemetrexed maintenance following induction therapy with platinum/ pemetrexed in patients with metastatic EGFR mutated non-small-cell lung cancer progressing after first-line treatment with afatinib as first tyrosine kinase inhibitor with respect to progression-free survival

Detailed Description
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Patients who have progressed after first-line treatment with afatinib as first tyrosine kinase inhibitor (TKI) will be screened while they are receiving second-line (induction) treatment consisting of cisplatin / carboplatin plus pemetrexed given in 21-day cycles. Patients who do not progress (i.e. complete or partial response, or stable disease - CR, PR or SD) after completion of at least three and not more than four chemotherapy cycles will be randomized (1:1 ratio) to receive maintenance therapy with either afatinib (40 mg/d or last tolerated dose during first-line treatment with afatinib as first TKI) or pemetrexed (500 mg/m2 or 375 mg/m2 if dose reduction was required every 21 days) until disease progression or treatment discontinuation because of patient decision or toxicity.

Official Title
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Biomarker Study Accompanying the AIO-TRK-0114 Study (MARBLE)

Conditions
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Non-small-cell Lung Cancer With Somatic EGFR Mutations

Intervention / Treatment
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* Drug: Afatinib
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in the AIO-TRK-0114 (MARBLE) study (EudraCT-No. 2014-001983-36) Written informed consent Exclusion Criteria: 1. Patients who do not meet the inclusion criterial of the AIO-TRK-0114 (MARBLE) study (EudraCT-No. 2014-001983-36)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, open-label, phase II study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Afatinib<br>Afatinib 40 mg/d (30, or 20 mg/d in case of dose reduction during 1st line treatment) | Drug: Afatinib<br> <br> |
| Experimental: Arm B: Pemetrexed<br>Pemetrexed 500 mg/m2 (375 mg/m² in case of dose reduction during induction therapy) i.v. on d1 of each 21-day cycle | Drug: Pemetrexed<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival in relation to exploratory biomarkers |  | until progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival in relation to exploratory biomarkers | Overall survival | continuous assessment | 
| Objective response rate | Objective response rate, clinical benefit rate (RECIST 1.1) | Assessed every 6 weeks for 24 weeks, then every 9 weeks |