Trametinib in Patients With Advanced Neurofibromatosis Type 1 (NF1)-Mutant Non-small Cell Lung Cancer

Stopped early · Phase 2

Conditions studied: Non-small Cell Lung Cancer

In brief

Phase II trial to evaluate trametinib in patients with locally advanced non-squamous, non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with progressive disease on at least one prior line of therapy.

Key facts

Study ID

NCT03232892

Run by

University of California, San Francisco

People needed

1

Starts

2018-02-13

Expected to finish

2019-09-11

Last updated by the study team

2019-12-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically or cytologically confirmed metastatic or unresectable locally advanced, non-squamous, NSCLC.
• Documented non-synonymous somatic mutation in NF1 in any tumor specimen or cell-free DNA assay by Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.
• Received at least one prior line of cancer therapy for the treatment of NSCLC; this should include at least one of the following: platinum (carboplatin or cisplatin) doublet chemotherapy (acceptable combinations include: paclitaxel, docetaxel, abraxane, pemetrexed, gemcitabine, vinorelbine, or etoposide), anti-PD1/PDL1 therapy (pembrolizumab, nivolumab, or atezolizumab), or appropriate targeted therapy in patients with activating EGFR (osimertinib, erlotinib, gefitinib, or afatinib), ALK (alectinib, crizotinib, ceritinib, brigatinib, or loralatinib), or ROS-1 (crizotininb or entrectinib) alterations; therapy may be given as monotherapy or in combination with other cancer therapy (e.g. bevacizumab, ipilumimab)
• Patients with a known activating mutation in epidermal growth factor receptor (EGFR) (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase inhibitor (TKI) (erlotinib, afatinib, or gefitinib). Patients whose tumors were found to have an EGFR T790M mutation must also have progressed or been intolerable to treatment with osimertinib.
• Patients with a known Anaplastic lymphoma kinase (ALK)-rearrangement must have progressed or been intolerant to treatment with at least one ALK TKI: crizotinib ceritinib, alectinib,brigatinib, or loralatinib
• Patients with a known ROS-1-rearrangement must have progressed or been intolerant to treatment with crizotinib or entrectinib
• Patients with PDL1 level of >= 50%, who do not have an ALK-rearrangement or EGFR-mutation, must have progressed or been intolerant to treatment with anti-PD1/PDL1 therapy (pembrolizumab, nivolumab, or atezolizumab)
• Documented disease progression or intolerance to treatment either during or after treatment with most recent therapy.
• Willingness to undergo research biopsy.
• Measurable disease defined by RECIST 1.1 criteria.
• Life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Age ≥ 18 years.
• Resolution of all acute toxic effects of prior chemotherapy, immunotherapy, radiotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 grade 1.
• Adequate baseline organ function defined as follows:
• Hematologic:
• Absolute neutrophil count: ≥ 1.2 x 10\^9/L
• Hemoglobin: ≥ 9 g/dL
• Platelets: ≥ 100 x 10\^9/L
• PT/INR and PTT: ≤ 1.5 x upper limit of normal (ULN)
• Hepatic:
• Albumin: ≥ 2.5 g/dL
• Total bilirubin: ≤ 1.5 x ULN
• AST and ALT: ≤ 2.5 x ULN
• Renal:

You may not qualify if…

• Known mutation in KRAS at position G12, G13, or Q61.
• Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases are allowed as long as they are stable for at least 28 days post-treatment.
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with trametinib . Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with trametinib, breastfeeding should be discontinued if the mother is treated with trametinib.
• History of another malignancy. Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer and/or subjects with indolent second malignancies are eligible.
• Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
• The subject has received cytotoxic chemotherapy, molecular targeted therapy, or immunotherapy within 21 days before the first dose of study drug (trametinib).
• Prior treatment with MEK inhibitor.
• History of interstitial lung disease or pneumonitis.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
• Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to study enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to study enrollment.
• History of retinal vein occlusion (RVO).
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV infection will be permitted).
• History or evidence of cardiovascular risk including any of the following:
• LVEF < LLN
• A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec;
• History or evidence of current clinically significant uncontrolled arrhythmias.
• Clarification: Subjects with atrial fibrillation controlled (defined as not requiring change in cardiac drug dosing, emergency room visit, or hospital admission) for > 30 days prior to dosing are eligible.
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study enrollment.
• History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association (NYHA).
• Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy;
• Patients with intra-cardiac defibrillators.

Where it is running

• University of California, San Francisco — San Francisco, California, United States

Full record on ClinicalTrials.gov

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