A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib
1 other identifier
interventional
24
1 country
7
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2017
Typical duration for phase_1
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2017
CompletedFirst Submitted
Initial submission to the registry
March 6, 2017
CompletedFirst Posted
Study publicly available on registry
March 10, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 18, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2020
CompletedResults Posted
Study results publicly available
February 8, 2022
CompletedApril 2, 2024
June 1, 2020
3.8 years
March 6, 2017
October 14, 2021
March 6, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
2 years
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.
2 years
Study Arms (1)
Trametinib 1.5mg + Erlotinib 75mg
EXPERIMENTALPhase 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) on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily or Trametinib 1.0mg + Erlotinib 100mg by mouth once daily.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- GlaxoSmithKlinecollaborator
Study Sites (7)
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memoral Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10021, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Helene Yu, MD
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Helena Yu, MD
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 6, 2017
First Posted
March 10, 2017
Study Start
March 1, 2017
Primary Completion
December 18, 2020
Study Completion
December 18, 2020
Last Updated
April 2, 2024
Results First Posted
February 8, 2022
Record last verified: 2020-06