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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ClinicalTrials.gov Identifier: NCT03076164 |
Recruitment Status :
Completed
First Posted : March 10, 2017
Results First Posted : February 8, 2022
Last Update Posted : February 8, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Lung Adenocarcinoma Lung Cancer Lung Cancer Metastatic Lung Cancer Stage IV Recurrent Lung Adenocarcinoma Recurrent Lung Cancer | Drug: Trametinib Drug: Erlotinib | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 24 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Trametinib 1.5mg + Erlotinib 75mg |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib |
Actual Study Start Date : | March 1, 2017 |
Actual Primary Completion Date : | December 18, 2020 |
Actual Study Completion Date : | December 18, 2020 |

Arm | Intervention/treatment |
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Experimental: Trametinib 1.5mg + Erlotinib 75mg
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.
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Drug: Trametinib
Trametinib 1.5mg once daily by mouth Drug: Erlotinib Erlotinib 75mg once daily by mouth |
- Participants Response Rate [ Time Frame: 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 [ Time Frame: 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03076164
United States, New Jersey | |
Memoral Sloan Kettering Cancer Center | |
Basking Ridge, New Jersey, United States, 07920 | |
Memorial Sloan Kettering Monmouth | |
Middletown, New Jersey, United States, 07748 | |
Memorial Sloan Kettering Bergen | |
Montvale, New Jersey, United States, 07645 | |
United States, New York | |
Memorial Sloan Kettering Commack | |
Commack, New York, United States, 11725 | |
Memoral Sloan Kettering Westchester | |
Harrison, New York, United States, 10604 | |
Memorial Sloan Kettering Cancer Center | |
New York, New York, United States, 10021 | |
Memorial Sloan Kettering Nassau | |
Uniondale, New York, United States, 11553 |
Principal Investigator: | Helena Yu, MD | Memorial Sloan Kettering Cancer Center |
Documents provided by Memorial Sloan Kettering Cancer Center:
Responsible Party: | Memorial Sloan Kettering Cancer Center |
ClinicalTrials.gov Identifier: | NCT03076164 |
Other Study ID Numbers: |
15-098 |
First Posted: | March 10, 2017 Key Record Dates |
Results First Posted: | February 8, 2022 |
Last Update Posted: | February 8, 2022 |
Last Verified: | June 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
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 |
erlotinib trametinib 15-098 |
Lung Neoplasms Adenocarcinoma Adenocarcinoma of Lung Recurrence Disease Attributes Pathologic Processes Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases |
Respiratory Tract Diseases Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Erlotinib Hydrochloride Trametinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |