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
Overview
- Phase
- Phase 1
- Intervention
- Dose escalation followed by treatment with MTD
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Afatinib
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
Intervention: Dose escalation followed by treatment with MTD
Outcomes
Primary Outcomes
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).
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.
Secondary Outcomes
- Determination of Dosage for Expansion Cohort in Part B(28 days)
- Objective Response Rate for Patients With EGFR T790M Mutations(From first drug administration until last drug administration, up to 420 days)
- 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))