Phase 1
Completed N=35
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
Source: ClinicalTrials.gov NCT01647711 ↗Enrolled (actual)
35
Serious AEs
40.0%
Results posted
Jan 2017
Primary outcomePrimary: Percentage of Participants With Dose Limiting Toxicities — 16.7; 0.0; 0.0; 0.0 Percentage of participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Dose Limiting Toxicities |
16.7; 0.0; 0.0; 0.0; 40.0 | — |
| PRIMARY Maximum Tolerated Dose |
160 | — |
| SECONDARY Objective Response Rate for Patients With EGFR T790M Mutations |
0.0; 14.3; 0.0; 0.0 | — |
| SECONDARY Cmax of Afatinib on Day 3 of Course 1 |
129; 155; 311; 313; 461 | — |
| SECONDARY Determination of Dosage for Expansion Cohort in Part B |
150 | — |
Eligibility Criteria
Inclusion criteria
Part A only:
- Patients with histologically confirmed advanced solid tumours that are metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients who refuse standard therapy are also eligible.
Part B only:
- Pathologically confirmed diagnosis of Stage IV (M1a or b) non-small cell lung cancer
- Documented Epidermal Growth Factor Receptor (EGFR) T790M mutation
- Progression of disease on a reversible tyrosine kinase inhibitor within 30 days of starting study drug. Loss of exposure to prior EGFR TKI should not be >30 days; any procedural delay in confirmation of progression is to be discussed with the BI Clinical Monitor.
Parts A and B:
- Evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Age >/= to 18 years
- Eastern Cooperative Group (ECOG) performance status 0-1
- Adequate organ function
- Recovered from any previous therapy-related toxicity to 0.47 seconds as measured during screening procedures
Data sourced from ClinicalTrials.gov (NCT01647711). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.