Clinical trial NCT03076164: A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib
Official title: A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Adenocarcinoma
Lung Cancer
Lung Cancer Metastatic
Lung Cancer Stage IV
Recurrent Lung Adenocarcinoma
Recurrent Lung Cancer
Keywords: erlotinib
trametinib
15-098
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2017-03-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Trametinib 1.5mg + Erlotinib 75mg
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Participants Response Rate
timeFrame: 2 years
measure: Number of Participants Evaluated for Toxicities
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memoral Sloan Kettering Cancer Center
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memoral Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Helena Yu, MD
role: PRINCIPAL_INVESTIGATOR
References: