Clinical Trials /

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

NCT03076164

Description:

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.

Related Conditions:
  • Lung Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 15-098
  • NCT ID: NCT03076164

Conditions

  • Lung Adenocarcinoma
  • Lung Cancer
  • Lung Cancer Metastatic
  • Lung Cancer Stage IV
  • Recurrent Lung Adenocarcinoma
  • Recurrent Lung Cancer

Interventions

DrugSynonymsArms
TrametinibTrametinib 1.5mg + Erlotinib 75mg
ErlotinibTrametinib 1.5mg + Erlotinib 75mg

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Trametinib 1.5mg + Erlotinib 75mgExperimentalPhase 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
  • Erlotinib

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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • erlotinib
  • trametinib
  • 15-098

Last Updated

March 9, 2017