A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib

Phase 1

Completed

• Conditions: Lung Cancer; Recurrent Lung Adenocarcinoma; Lung Adenocarcinoma; Lung Cancer Metastatic; Lung Cancer Stage IV; Recurrent Lung Cancer
• Interventions: Drug: Trametinib; Drug: Erlotinib

• Registration Number: NCT03076164
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-03-01
• Study First Submitted: 2017-03-06
• Study First Submitted QC: 2017-03-09
• Study First Posted: 2017-03-10
• Status Verified: 2020-06
• Primary Completion: 2020-12-18
• Study Completion: 2020-12-18
• Results First Submitted: 2021-10-14
• Results First Submitted QC: 2022-01-12
• Results First Posted: 2022-02-08
• Last Update Submitted: 2024-03-06
• Last Update Posted: 2024-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trametinib 1.5mg + Erlotinib 75mg	Erlotinib	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) on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily or Trametinib 1.0mg + Erlotinib 100mg by mouth once daily.
Trametinib 1.5mg + Erlotinib 75mg	Trametinib	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) on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily or Trametinib 1.0mg + Erlotinib 100mg by mouth once daily.

Primary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (7)

Memorial Sloan Kettering Commack; 🇺🇸 Commack, New York, United States

Memoral Sloan Kettering Cancer Center; 🇺🇸 Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Nassau; 🇺🇸 Uniondale, New York, United States

Memoral Sloan Kettering Westchester; 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering Bergen; 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Monmouth; 🇺🇸 Middletown, New Jersey, United States