Lung Adenocarcinoma, Lung Cancer, Lung Cancer Metastatic, Lung Cancer Stage IV, Recurrent Lung Adenocarcinoma, Recurrent Lung Cancer
Conditions
Keywords
erlotinib, trametinib, 15-098
Brief summary
The purpose of this study is to determine the safety, tolerability and overall response rate of trametinib when given in combination with erlotinib in patients with Stage IV or recurrent lung adenocarcinoma that cannot be treated with curative intent.
Interventions
DRUGTrametinib
Trametinib 1.5mg once daily by mouth
DRUGErlotinib
Erlotinib 75mg once daily by mouth
Sponsors
GlaxoSmithKline
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Trametinib 1.5mg + Erlotinib 75mg
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologic evidence of advanced stage IV or recurrent lung adenocarcinoma reviewed at MSKCC * Somatic activating mutation in EGFR Radiographic progression during treatment with erlotinib. * Any number of prior chemotherapy regimens is permitted. * Measurable (RECIST 1.1) indicator lesion not previously irradiated * KPS \>/= 70% * Age \>18 years old * Must have undergone biopsy after development of acquired resistance to erlotinib with available archived tissue (equivalent of \> 10 unstained slides) * Left ventricular Ejection Fraction \>/= the lower limit of normal by ECHO or MUGA * Adequate organ function: * AST, ALT \</= 2.5 x ULN * Total bilirubin \</= 1.5 x ULN * Albumin\>/=2.6g/dL - Creatinine \< 1.5 x ULN OR calculated creatinine clearance \>/=50mL/min * Absolute neutrophil count (ANC) \>/= 1,200 cells/mm3 * Hemoglobin\>/=9.0 g/dL * Platelets \>/=100,000/mm3
Exclusion criteria
* Patients with symptomatic brain metastasis requiring escalating doses of steroids * Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management due to medications or a medical condition such as Crohn's disease or malabsorption * Pregnant or lactating women * Any type of systemic therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol except for a EGFR TKI * Patients who have received prior treatment with a MEK inhibitor * Any major surgery or extensive radiotherapy within 21 days of starting treatment on protocol. * A history of clinically significant interstitial lung disease or pneumonitis * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study administration, New York Heart Association Class III or IV congestive heart failure, or symptomatic uncontrolled Arrythmias, prolonged corrected QT interval \>480msec, treatment refractory hypertension, presence of a cardiac defibrillator * History of central serous retinopathy or retinal vein occlusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Response Rate | 2 years | Response and progression of disease will be evaluated in this study using interval imaging every 8 weeks with CT scan of the chest and imaging of any other target lesion with response evaluated by RECIST 1.1. |
| Number of Participants Evaluated for Toxicities | 2 years | Safety and tolerability will be evaluated by systematic and regular toxicity evaluations. Toxicity will be graded according to NCI CTCAE version 4.0. |
Countries
United States
Participant flow
Pre-assignment details
This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort.
Participants by arm
| Arm | Count |
|---|---|
| Trametinib 1.5mg + Erlotinib 75mg Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) daily doses of 75mg erlotinib and 1.5mg trametinib This treatment regimen was already assessed in a previous study. The phase 1 portion was a safety lead-in of a slight modification of the previously established combination dosing. As a consequence, we only did a safety lead in of one dose level that was determined to be the phase 2 dose and we rolled all the phase 1 patients into the phase 2 cohort. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Trametinib 1.5mg + Erlotinib 75mg |
|---|---|
| Age, Continuous | 62 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 20 / 24 |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 6 / 24 |
Outcome results
Primary
Number of Participants Evaluated for Toxicities
Safety and tolerability will be evaluated by systematic and regular toxicity evaluations. Toxicity will be graded according to NCI CTCAE version 4.0.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trametinib 1.5mg + Erlotinib 75mg | Number of Participants Evaluated for Toxicities | 24 Participants |
Primary
Participants Response Rate
Response and progression of disease will be evaluated in this study using interval imaging every 8 weeks with CT scan of the chest and imaging of any other target lesion with response evaluated by RECIST 1.1.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trametinib 1.5mg + Erlotinib 75mg | Participants Response Rate | Stable Disease | 11 participants |
| Trametinib 1.5mg + Erlotinib 75mg | Participants Response Rate | Progression of disease | 4 participants |
| Trametinib 1.5mg + Erlotinib 75mg | Participants Response Rate | Not Entered | 8 participants |
| Trametinib 1.5mg + Erlotinib 75mg | Participants Response Rate | Partial Response | 1 participants |