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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03076164
• Other study ID #: 15-098
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 1, 2017
• Est. completion date: December 18, 2020

Study information

• Verified date: June 2020
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 18, 2020
• Est. primary completion date: December 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Lung Adenocarcinoma
• Lung Cancer
• Lung Cancer Metastatic
• Lung Cancer Stage IV
• Lung Neoplasms
• Recurrence
• Recurrent Lung Adenocarcinoma
• Recurrent Lung Cancer

Intervention

Drug:
• Trametinib
Trametinib 1.5mg once daily by mouth
• Erlotinib
Erlotinib 75mg once daily by mouth

Locations

Country	Name	City	State
United States	Memoral Sloan Kettering Cancer Center	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Memoral Sloan Kettering Westchester	Harrison	New York
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	2 years
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.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center