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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

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ClinicalTrials.gov Identifier: NCT03076164
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : August 2, 2018
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Study Description
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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.

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
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
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

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Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: Trametinib
Trametinib 1.5mg once daily by mouth

Drug: Erlotinib
Erlotinib 75mg once daily by mouth


Outcome Measures
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Primary Outcome Measures :
  1. Overall 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.

  2. 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 ]
    Safety and tolerability will be evaluated by systematic and regular toxicity evaluations. Toxicity will be graded according to NCI CTCAE version 4.0.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Helena Yu, MD 646-888-4274 yuh@mskcc.org
Contact: Gergory Riely, MD, PhD 646-888-4199

Locations
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United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Helena Yu, MD    646-888-4274      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Helena Yu, MD    646-888-4274      
Memoral Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Helena Yu, MD    646-888-4274      
Memorial Sloan Kettering Rockville Centre Recruiting
Rockville Centre, New York, United States, 11570
Contact: Helena Yu, MD    646-888-4274      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
GlaxoSmithKline
Investigators
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Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center
More Information
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Additional Information:
Memorial Sloan Kettering Cancer Center  This link exits the ClinicalTrials.gov site

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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03076164     History of Changes
Other Study ID Numbers: 15-098
First Posted: March 10, 2017    Key Record Dates
Last Update Posted: August 2, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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

Keywords provided by Memorial Sloan Kettering Cancer Center:
erlotinib
trametinib
15-098

Additional relevant MeSH terms:
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Lung Neoplasms
Adenocarcinoma
Adenocarcinoma of Lung
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