Clinical trial NCT01836341: Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Keywords: Afatinib
Cisplatin
Carboplatin
Pemetrexed
Radiation therapy
EGFR mutation
12-279
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
name: National Comprehensive Cancer Network
First posted: 2013-04-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 1 year
Secondary outcomes:
measure: local control rate
timeFrame: at 1 year and at 2 years
measure: tolerability of adjuvant afatinib
timeFrame: at 3 months
measure: median progression free survival
timeFrame: 2 years
measure: median overall survival
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jamie E. Chaft, MD
role: PRINCIPAL_INVESTIGATOR
References: