A Study of Intermittent, High-dose Afatinib to Determine the Maximal Tolerated Dose and Assess Activity of This Dose Against Non-small Cell Lung Cancer With T790M Mutations
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|ClinicalTrials.gov Identifier: NCT01647711|
Recruitment Status : Completed
First Posted : July 23, 2012
Results First Posted : January 31, 2017
Last Update Posted : January 31, 2017
This trial is divided into Part A and Part B. The primary objective of Part A is to establish the Maximal Tolerated Dose of intermittent high dose afatinib. The primary objective of Part B is to assess the response rate of patients with non-small cell lung cancer with EGFR T790M mutations to a dose of intermittent afatinib established in Part A.
The secondary objective is to explore tumor response and tumor-derived biological markers of response to afatinib, as well as pharmacokinetic parameters of afatinib.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Non-Small-Cell Lung||Drug: Dose escalation followed by treatment with MTD||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b Study of Intermittent Administration of High Doses of the Irreversible EGFR Inhibitor Afatinib as a Means of Achieving Plasma Levels Active Against Non-small Cell Lung Cancer With Known T790M Mutations|
|Study Start Date :||July 2012|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||September 2015|
Establish the Maximal Tolerated Dose of a pulsatile, high-dose regimen of afatinib in patients with advanced solid tumors followed by treatment at that dose or a lower dose in patients with stage IV non-small cell lung cancer harboring EGFR T790M mutations who have progressed on therapy with a reversible tyrosine kinase inhibitor
Drug: Dose escalation followed by treatment with MTD
Fixed 3+3 dose escalation; expansion of MTD cohort
- Percentage of Participants With Dose Limiting Toxicities [ Time Frame: 28 days ]Percentage of participants with Dose Limiting Toxicities (DLTs), based on investigator assessment, for determination of Maximum Tolerated Dose (MTD). MTD was defined as the dose in which less than 2 of up to 6 patients developed a DLT.
- Maximum Tolerated Dose [ Time Frame: 28 days ]Maximum Tolerated Dose (MTD) was defined as the dose in which less than 2 of up to 6 patients developed a Dose Limiting Toxicity (DLT).
- Objective Response Rate for Patients With EGFR T790M Mutations [ Time Frame: From first drug administration until last drug administration, up to 420 days ]
Objective response rate for patients with Epidermal Growth Factor Receptor (EGFR) T790M mutations. Objective response was defined as Complete Response (CR): Disappearance of all target lesion or Partial Response and (PR): >=30% decrease in the sum of the longest diameter of target lesions, according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
This endpoint was originally planned to be analysed in part B of the study, however as no participants were treated in part B the analysis was performed on the part A participants.
- Cmax of Afatinib on Day 3 of Course 1 [ Time Frame: 47 hours (h) 55 minutes (min), 49h, 50h, 51h, 52h, 53h, 54h, 55h after first dose administration (on day 3 of course 1) ]Maximum measured concentration (Cmax) of afatinib as determined on day 3 of course 1 for patients in Part A
- Determination of Dosage for Expansion Cohort in Part B [ Time Frame: 28 days ]Determination of dosage for expansion cohort in Part B. Dosage was the MTD or less depending on tolerability.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01647711
|United States, Colorado|
|Boehringer Ingelheim Investigational Site|
|Aurora, Colorado, United States|
|United States, Massachusetts|
|Boehringer Ingelheim Investigational Site|
|Boston, Massachusetts, United States|
|Study Chair:||Boehringer Ingelheim||Boehringer Ingelheim|