Trial of Continuous Once Daily Oral Treatment Using BIBW 2992 (Afatinib) Plus Sirolimus (Rapamune®) in Patients With Non-small Cell Lung Cancer Harbouring an EGFR Mutation and/or Disease Progression Following Prior Erlotinib or Gefitinib
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT00993499
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this trial is to identify the Maximum Tolerated Dose of BIBW 2992 therapy when given continuously in combination with Sirolimus.
The MTD will be based on the Dose Limiting Toxicity information collected during the first two cycles.
Overall safety, pharmacokinetics and anti-tumour efficacy will be evaluated as secondary objectives.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BIBW 2992 + Sirolimus Sirolimus (rapamycin) Dose escalation of the combination BIBW 2992 plus Sirolimus. BIBW 2992 + Sirolimus BIBW 2992 Dose escalation of the combination BIBW 2992 plus Sirolimus.
- Primary Outcome Measures
Name Time Method Occurrence of Dose Limiting Toxicities (DLT) 2 first cycles, 56 days Number of participants with of dose limiting toxicities (DLT)
- Secondary Outcome Measures
Name Time Method Occurrence of Adverse Events According to CTCAE, Version 3.0 From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days Percentage of participants with adverse events according to highest Common Terminology Criteria for Adverse Events (CTCAE) grade, version 3.0
Best Overall Response From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days Best overall response (unconfirmed) according to RECIST v1.1
Objective Response From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days Rate of (unconfirmed) objective response, defined as complete response (CR) or partial response (PR) according to RECIST v1.1
Rate of Disease Control From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days Rate of (unconfirmed) disease control defined as CR, PR, or stable disease (SD), according to RECIST v1.1
Exploratory Examination of EGFR Mutations (Exons 19, 20 and 21 and Others) in Serum/Plasma DNA and Tumour DNA. Multiple time points during the trial Exploratory examination of Epidermal growth factor (receptor)(EGFR) mutations (Exons 19, 20 and 21 and others) in serum/plasma DNA and tumour DNA.
This endpoint was not analysed in the study report as the available data was too limited.Maximum Measured Plasma Concentration of Afatinib at Steady State (Cmax,ss) 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib Maximum measured plasma concentration of Afatinib at steady state (Cmax,ss)
AUC of Afatinib at Steady State Over the Dosing Interval τ (AUCτ,ss) 24 hours (h), 311h 55minutes (min), 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h and 336h after first administration of afatinib Area under the curve (AUC) of Afatinib at steady state over the dosing interval τ (AUCτ,ss) for afatinib.
Maximum Measured Plasma Concentration of Sirolimus at Steady State (Cmax,ss) 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib Maximum measured plasma concentration of sirolimus at steady state (Cmax,ss)
AUC of Sirolimus at Steady State Over the Dosing Interval τ (AUCτ,ss) 24 hours (h) 5 minutes (min), 24h, 23h, 22h, 20h, 18h, 16h, 5min before first afatinib administration and 144h, 311h 55min, 312h, 313h, 314h, 315h, 316h, 317h, 318h, 320h, 336h, 480h after first administration of afatinib Area under the curve (AUC) of sirolimus at steady state over the dosing interval τ (AUCτ,ss) for afatinib.
Percentage of Patients With Drug-related AEs From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days Percentage of patients with drug-related adverse events (AEs).
Frequency of Patients With Possible Clinically-significant Abnormalities in Liver Enzymes or Total Bilirubin From first trial medication intake in the first treatment course until last trial medication intake plus 28 days, up to 367 days Evaluation of laboratory parameters included assessment of the frequency of patients with ALT and AST elevations concurrent with elevated bilirubin and indicative of Hy's law cases.
Trial Locations
- Locations (8)
1200.70.34002 Boehringer Ingelheim Investigational Site
🇪🇸Zaragoza, Spain
1200.70.34009 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1200.70.34006 Boehringer Ingelheim Investigational Site
🇪🇸Girona, Spain
1200.70.34007 Boehringer Ingelheim Investigational Site
🇪🇸L'Hospitalet de Llobregat (Barcelona), Spain
1200.70.34005 Boehringer Ingelheim Investigational Site
🇪🇸Majadahonda (Madrid), Spain
1200.70.34008 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1200.70.34001 Boehringer Ingelheim Investigational Site
🇪🇸Badalona (Barcelona), Spain
1200.70.34004 Boehringer Ingelheim Investigational Site
🇪🇸Valencia, Spain