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

Phase 1

Completed

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: Dose escalation followed by treatment with MTD

• Registration Number: NCT01647711
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-07-16
• Study First Submitted QC: 2012-07-19
• Study First Posted: 2012-07-23
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Results First Submitted: 2016-09-22
• Status Verified: 2016-12
• Results First Submitted QC: 2016-12-08
• Last Update Submitted: 2016-12-08
• Results First Posted: 2017-01-31
• Last Update Posted: 2017-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Afatinib	Dose escalation followed by treatment with MTD	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

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	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).
Percentage of Participants With Dose Limiting Toxicities	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.

Secondary Outcome Measures

Name	Time	Method
Determination of Dosage for Expansion Cohort in Part B	28 days	Determination of dosage for expansion cohort in Part B. Dosage was the MTD or less depending on tolerability.
Objective Response Rate for Patients With EGFR T790M Mutations	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	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

Trial Locations

Locations (1)

Boehringer Ingelheim Investigational Site; 🇺🇸 Boston, Massachusetts, United States