Stage IIIA Non-Small Cell Lung Cancer, Stage IIIB Non-Small Cell Lung Cancer
Conditions
Brief summary
This phase II trial studies how well erlotinib hydrochloride works before surgery in treating patients with stage III non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the rate of mediastinal nodal clearance and complete pathological response after neoadjuvant erlotinib (erlotinib hydrochloride) in patients with epidermal growth factor receptor (EGFR) mutated stage III non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To determine the progression free survival in patient population of EGFR mutated stage III NSCLC patients who are treated with neoadjuvant erlotinib therapy. II. To determine the overall survival. III. To estimate the overall response rate from neoadjuvant erlotinib. IV. To estimate the surgical resection rate. V. To evaluate the safety of neoadjuvant erlotinib. TERTIARY OBJECTIVES: I. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of neoadjuvant erlotinib. OUTLINE: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 2 months and then undergo thoracotomy. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 5 years.
Interventions
DRUGErlotinib Hydrochloride
Given PO
PROCEDURETherapeutic Conventional Surgery
Undergo thoracotomy
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Albert Einstein College of Medicine
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
* Pathologically proven (either histologic or cytologic) diagnosis of stage IIIA or IIIB non-small cell lung cancer; (according to American Joint Committee on Cancer \[AJCC\] staging, 7th edition) within 4 weeks of registration; the patient should have histologically or cytologically confirmed N2 disease * Activating mutation in EGFR * No prior chemotherapy or radiation for lung cancer * Patients may be potentially resectable or unresectable * Stage III A or B disease, including no distant metastases- based on following diagnostic workup: * History/physical examination prior to registration * Computed tomography (CT) scan of the chest or positron emission tomography (PET) scan within 28 days of study entry * CT scan of abdomen or magnetic resonance imaging (MRI) of abdomen or PET scan within 28 days of study entry * An MRI of the brain or head CT scan with contrast within 28 days of study entry * Total body PET scan within 28 days of study entry * Mediastinoscopies are highly recommended * Patients must have measurable or evaluable disease * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) \>= 1,500 cells/ul * Platelets \>= 100,000 cells/ul * Hemoglobin \>= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= g/dl is acceptable) * Serum creatinine =\< 1.5 x upper limit of normal (ULN) * Total bilirubin \< 2.0 times the institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x the ULN * Women of childbearing potential must have: * A negative serum or urine pregnancy test (sensitivity =\< 25 IU human chorionic gonadotropin \[HCG\]/L) within 72 hours prior to the start of study drug administration * Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy * Ability to take oral medication * Patient must sign study specific informed consent prior to study entry
Exclusion criteria
* Pleural or pericardial effusion * Pleural effusions allowed if one of the following conditions are met: 1) negative cytology after adequate sampling by thoracentesis 2) effusion seen on CT scan but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance * Severe, active co-morbidity, defined as follows: * Cardiac symptoms; any of the following should be considered for exclusion: * Uncontrolled angina, congestive heart failure or myocardial infarction (MI) within (6 months) * Diagnosed congenital long QT syndrome * Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) * Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (\> 450 msec) * History of significant bleeding disorder unrelated to cancer, including: * Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) * Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) * Ongoing or recent (=\< 3 months) significant gastrointestinal bleeding * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness * Men and women who: * Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or women who: * Have a positive pregnancy test at baseline, or * Are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of Mediastinal Nodal Clearance, Defined as Pathologically Negative N2 Disease in the Final Surgical Resection Specimen or Mediastinoscopy | 3 years 9 months |
Countries
United States
Participant flow
Recruitment details
The patients were enrolled on 11/7/2013, 5/2014, and 9/24/2014.
Pre-assignment details
The study was difficult to enroll and eventually terminated/closed.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Erlotinib Hydrochloride and Thoracotomy) Patients receive erlotinib hydrochloride PO QD for 2 months and then undergo thoracotomy.
Erlotinib Hydrochloride: Given PO
Therapeutic Conventional Surgery: Undergo thoracotomy
Laboratory Biomarker Analysis: Correlative studies | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Treatment (Erlotinib Hydrochloride and Thoracotomy) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 3 |
| other Total, other adverse events | 1 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Rate of Mediastinal Nodal Clearance, Defined as Pathologically Negative N2 Disease in the Final Surgical Resection Specimen or Mediastinoscopy
Time frame: 3 years 9 months
Population: The study was closely prematurely due to poor accrual. No final analysis was performed due to very low number of subjects.