Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
The purpose of this Phase I study is to test the safety of combining afatinib with standard chemotherapy and radiation. The drug afatinib will be given before the chemotherapy and radiation therapy to shrink the tumor and evaluate how afatinib affects the patient. This study will then test the safety of afatinib at different dose levels when combined with the chemotherapy drugs cisplatin or carboplatin, and pemetrexed. These treatments will be given during radiation treatment and the drug afatinib will be continued after chemotherapy and radiation.
Non-small Cell Lung Cancer
Radiation: Radiation therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose-Finding Study Of Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation|
- maximum tolerated dose [ Time Frame: 1 year ] [ Designated as safety issue: No ]This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.
- local control rate [ Time Frame: at 1 year and at 2 years ] [ Designated as safety issue: No ]will be determined as the proportion of patients who start the concurrent phase who are alive and free of local failure.
- tolerability of adjuvant afatinib [ Time Frame: at 3 months ] [ Designated as safety issue: No ]Tolerability will be defined by in terms of dose reductions, delays and discontinuations of patients who have not had disease progression or death.
- median progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]PFS is defined as the duration of time from start of treatment to time of progression of disease or death, whichever occurs first.
- median overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]will be calculated using Kaplan-Meier estimates among all patients enrolled.
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Afatinib w Cisplatin Pemetrexed Chemoradiation
induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation*
*afatinib dose levels: 20mg daily, 30mg daily & 40mg daily (3+3 design) Then adjuvant afatinib x 2 years
|Drug: Afatinib Drug: Cisplatin Drug: Carboplatin Drug: Pemetrexed Radiation: Radiation therapy|