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About
This phase I trial is studying the safety, side effects, and best dose of gilteritinib in treating patients with stage IV ALK positive non-small cell lung cancer (NSCLC) who have progressed on other treatments. While there are many approved targeted drugs for ALK NSCLC, resistance to these drugs frequently occur. Giltertinib is a drug that is already FDA approved for the treatment of a specific type of leukemia. However, studies using ALK positive lung cancer cells demonstrate activity of gilteritinib against these resistant cells. Therefore, in this clinical trial, the investigators plan to study the effect of giltertinib in patients with ALK NSCLC.
Enrollment
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Volunteers
Inclusion criteria
Stage IV (American Joint Committee on Cancer [AJCC] 8th edition) non-small cell lung cancer with an oncogenic ALK fusion
Histologies include adenocarcinoma, squamous cell carcinoma, and adenosquamous adenocarcinoma
The presence of an oncogenic ALK fusion established from any Clinical Laboratory Improvement Act (CLIA) certified laboratory
The patient must belong to one of the following treatment cohorts.
Age ≥ 18
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) ≥ 1500/mcL
Platelets ≥ 100,000/mcL
Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
Measured or calculated creatinine clearance (CrCl) ≥ 50mL/min (calculated per Cockcroft-Gault formula)
Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) (per institutional guidelines) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
Albumin ≥ 2.5g/dL
Female subject of childbearing potential should have a negative serum pregnancy test within 21 days of enrollment prior to receiving the first dose of study medication
Female subjects of childbearing potential must be willing to use a highly effective method of contraception for the course of the study, through 180 days after the last dose of study medication. Note: Abstinence is acceptable, if patient documents that this is their usual lifestyle or preferred contraception method
Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 4 months after the last dose of study therapy. Note: Abstinence is acceptable, if patient documents that this is their usual lifestyle or preferred contraception method
Ability to swallow pills orally and per investigator's assessment, do not have any significant issues limiting absorption of drug
Ability to understand and the willingness to sign a written informed consent
Measurable disease per RECIST v1.1 criteria assessed per screening imaging
If a cancerous lesion is easily and safely accessible, a pre-treatment biopsy of this lesion is strongly encouraged but NOT required prior to first dose of gilteritinib. Archival or fresh tissue biopsy may be used as long as it was obtained prior to cycle 1 day 1 (C1D1)
At least 7 days must have elapsed since last anti-neoplastic TKI, chemotherapy, immunotherapy, or investigational agent prior to the first dose of gilteritinib
Exclusion criteria
Received palliative radiation within 7 days of enrollment
Received prior therapy with a FLT3 inhibitor
Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. Note: the time requirement for no evidence of disease for 5 years does not apply to the NSCLC tumor for which a subject is enrolled in the study. The time requirement also does not apply to subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers
Has known active and symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
If a patient is found to have new/enlarging brain metastases on the screening MRI, the patient may be monitored closely and radiation could be delayed if the patient has no symptoms, there is no vasogenic edema, and there is no evidence of midline shift.
Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with informed consent through 180 days after the last dose of trial treatment
Has Child-Pugh class C cirrhosis from any cause
Mean triplicate screening electrocardiogram (EKG) corrected QT (QTc) > 480 ms
Grade 3 or 4 NYHA (New York Heart Association) congestive heart failure, unless screening echocardiogram obtained prior to enrollment showed a LVEF (left ventricular ejection fraction) ≥ 45%
Surgery within 4 weeks prior to first study dose
Requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A
Requires treatment with concomitant drugs that are strong inhibitors or inducers of P-glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the patient
Requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the patient
Active/untreated hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; patients with treated HBV and HCV are allowed as long as they meet the AST/ALT and bilirubin criteria
Known hypersensitivity to gilteritinib or any of the excipients
Active and clinically significant pancreatitis
Primary purpose
Allocation
Interventional model
Masking
30 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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