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About
This phase II trial studies how well infigratinib works in treating solid tumors that have spread to other places in the body (advanced or metastatic) in patients with FGFR gene mutations such as FGFR1-3 gene fusions or other FGFR genetic alterations. Mutations are any changes in the genetic material (DNA) of a cell. FGFR proteins are involved in cell division, cell maturation, formation of new blood vessels, wound healing, and bone growth, development, and maintenance. FGFR mutations can cause the FGFR protein to become over-active in diseases such as cancer. Infigratinib may stop the growth of tumor cells by blocking FGFR proteins in these tumors.
Full description
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of single agent infigratinib in patients with advanced or metastatic solid tumors of any histologic classification with FGFR1-3 gene fusions/translocations or other FGFR genetic alterations (with and without prior therapy with different FGFR inhibitor).
II. To understand response rate and potential for infigratinib to benefit patients who have FGFR alterations including point mutations, insertions/deletions and amplifications in different solid tumor types.
SECONDARY OBJECTIVES:
I. To further evaluate the efficacy of single agent infigratinib. II. To characterize the safety and tolerability of single agent infigratinib. II. To evaluate benefit of infigratinib in patients who have received one prior FGFR inhibitor.
EXPLORATORY OBJECTIVES:
I. To detect biomarkers of resistance to infigratinib treatment through tumor sequencing.
II. To develop a circulating tumor deoxyribonucleic acid (DNA) (ctDNA) or liquid biopsy assay optimized for monitoring response to infigratinib and detecting emerging resistance mutations to infigratinib.
OUTLINE:
Patients receive infigratinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients who complete study treatment for any reason other than disease progression are followed for 30 days, every 8 weeks until disease progression, and then every 4 months for 1 year. All other patients are followed for 30 days, and then every 4 months for 1 year.
Enrollment
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Volunteers
Inclusion criteria
Patients with histologically or cytologically confirmed advanced or metastatic solid tumors of any histologic classification at the time of diagnosis
Written documentation of local or central Clinical Laboratory Improvement Act (CLIA)-certified laboratory determination of FGFR gene fusions/translocations or activating mutations
The study is open to solid tumors in the following cohorts:
Evidence of measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Patients must have received at least one prior SOC regimen for advanced/metastatic cancer. Patient should have had evidence of progressive disease following their prior regimen, or if prior treatment was discontinued due to toxicity must have continued evidence of measurable or evaluable disease. Patients who have received prior treatment with an alternate FGFR inhibitor are still eligible for the study
Patients with primary central nervous system (CNS) cancer or CNS metastases are excluded (because it is unclear how much CNS penetration the drug has). However, asymptomatic patients with history of successfully treated CNS metastases with surgery or radiation and follow up imaging showing stability, can be eligible
Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (patients with ECOG performance status of 2 may be considered on a case-by-case basis after discussion with QED Therapeutics)
Able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Ethics Committee (EC)
Recovery from adverse events of previous systemic anti-cancer therapies to baseline or grade 1, except for:
Able to swallow and retain oral medication
Willing and able to comply with scheduled visits, treatment plan and laboratory tests
Exclusion criteria
Patients who have therapies available that are known to confer a clinical benefit will be excluded from the study
Neurological symptoms related to underlying disease requiring increasing doses of corticosteroids. Note: Steroid use for management of CNS tumors is allowed but must be at a stable dose for at least 2 weeks preceding study entry
History of another primary malignancy except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study or affect survival
Any other medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
Current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination
History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc
Treatment with any of the following anti-cancer therapies prior to the first dose of infigratinib within the stated timeframes:
Patients who are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration are excluded. Patients are not permitted to receive enzyme-inducing anti-epileptic drugs
Consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products within 7 days prior to first dose
Use of medications that are known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose
Use of amiodarone within 90 days prior to first dose
Current use of therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulants. Heparin and/or low molecular weight heparins are allowed
Absolute neutrophil count (ANC) =< 1,000/mm^3 (1.0 x 10^9/L)
Platelets =< 75,000/mm^3 (75 x 10^9/L)
Hemoglobin =< 9.0 g/dL
Total bilirubin >= 1.5 x upper limit of normal (ULN) unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >= 3 x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Alkaline phosphatase >= 2.5 x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Calculated or measured creatinine clearance of < 40 mL/min
Calcium-phosphate homeostasis:
Clinically significant cardiac disease including any of the following:
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include:
Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of the study drug and should not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid
Primary purpose
Allocation
Interventional model
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17 participants in 1 patient group
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Central trial contact
Shona Taylor; The Ohio State University Comprehensive Cancer Center
Data sourced from clinicaltrials.gov
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