Non-small Cell Lung Cancer
Conditions
Keywords
Afatinib, Cisplatin, Carboplatin, Pemetrexed, Radiation therapy, EGFR mutation, 12-279
Brief summary
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.
Interventions
DRUGAfatinib
DRUGCisplatin
DRUGCarboplatin
DRUGPemetrexed
RADIATIONRadiation therapy
Sponsors
Boehringer Ingelheim
National Comprehensive Cancer Network
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unresectable or inoperable, stage III or locoregional recurrence without evidence of distant, metastatic disease * Pathologic confirmation of NSCLC at MSKCC * Documentation of a sensitizing EGFR mutation * Age ≥ 18 years * No contraindication to definitive thoracic radiation therapy with concurrent chemotherapy Adequate organ function as defined by: * Calculated creatinine clearance≥ 45 mL/min (by Cockcroft-Gault) * Total bilirubin less than 1.5 x ULN (unless known Gilbert's disease) and AST/ALT less than 3 x ULN * Absolute neutrophil count greater than 1500/mm3 * Platelet count greater than 100,000/mm3 * Women of childbearing age must have a negative blood pregnancy test * Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months there after
Exclusion criteria
* Prior chemotherapy or radiation therapy for this lung cancer (history of prior lung cancer that has been treated and deeded inactive by the clinician is acceptable) * Ineligible for cisplatin or carboplatin per medical oncologist * Ineligible for pemetrexed per medical oncologist * Greater than minimal, exudative, or malignant pleural effusion * Calculated creatinine clearance by Cockcroft & Gault method ≤45 ml/min * Unstable congestive heart failure * Ejection fraction \<50% as assessed by MUGA or echocardiogram * Interstitial lung disease * Patient requiring on-going treatment with a potent inhibitor (cyclosporin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital with quinidine, ritonavir, valspodar, verapamil) or inducer of P-gp (St. John's wort or rifampin) * Women who are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximum tolerated dose | 1 year | This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| local control rate | at 1 year and at 2 years | 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 | at 3 months | 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 | 2 years | 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 | 2 years | will be calculated using Kaplan-Meier estimates among all patients enrolled. |
Outcome results
None listed