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

Primary Purpose

Lung Adenocarcinoma, Lung Cancer, Lung Cancer Metastatic

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Trametinib
Erlotinib
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Adenocarcinoma focused on measuring erlotinib, trametinib, 15-098

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memoral Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Monmouth
  • Memorial Sloan Kettering Bergen
  • Memorial Sloan Kettering Commack
  • Memoral Sloan Kettering Westchester
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trametinib 1.5mg + Erlotinib 75mg

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
March 6, 2017
Last Updated
January 12, 2022
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT03076164
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
December 18, 2020 (Actual)
Study Completion Date
December 18, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Adenocarcinoma, Lung Cancer, Lung Cancer Metastatic, Lung Cancer Stage IV, Recurrent Lung Adenocarcinoma, Recurrent Lung Cancer
Keywords
erlotinib, trametinib, 15-098

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Trametinib 1.5mg + Erlotinib 75mg
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Trametinib 1.5mg + Erlotinib 75mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Trametinib
Intervention Description
Trametinib 1.5mg once daily by mouth
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Intervention Description
Erlotinib 75mg once daily by mouth
Primary Outcome Measure Information:
Title
Participants Response Rate
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.
Time Frame
2 years
Title
Number of Participants Evaluated for Toxicities
Description
Safety and tolerability will be evaluated by systematic and regular toxicity evaluations. Toxicity will be graded according to NCI CTCAE version 4.0.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helena Yu, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memoral Sloan Kettering Cancer Center
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memorial Sloan Kettering Monmouth
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memoral Sloan Kettering Westchester
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan Kettering Nassau
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
http://www.mskcc.org
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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