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About
The purpose of the study is identify the dose(s) of infigratinib to use in combination with tamoxifen to treat patients with a particular type of advanced breast cancer (hormone receptor-positive, HER2-negative, FGFR-altered breast cancer)
Full description
Primary Objective: Determine the maximum (no greater than 125 mg) dose of infigratinib used in combination with the FDA-approved dose and schedule of tamoxifen (Cohort 1) in terms of the number of dose-limiting toxicities observed in the first 2 cycles of therapy in subjects with hormone receptor-positive, HER2-negative advanced breast cancer.
Secondary Objective:
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Cohort 2 only: Measurable disease, as defined by RECIST v1.1.
≥ 18 years old
Eastern Cooperative Oncology Group (ECOG) 0 to 2
Prior cancer therapy (except for endocrine therapy, denosumab, or bisphosphonates) must be discontinued for 2 weeks prior to initiation of study drugs. Recovery from adverse events of previous cancer therapies to baseline or Grade 1 except for alopecia or stable Grade 2 neuropathy. Radiotherapy must also be completed at least 2 weeks prior to initiation of study drugs
Absolute neutrophil count (ANC) ≥ 1,000/mm3
Platelets ≥ 75,000/mm3
Hemoglobin ≥ 9.0 g/dL
Total bilirubin ≤ 1.8 mg/dL (unless documented Gilbert's disease)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 90 U/L
Estimated glomerular filtration rate (GFR) ≥ 45 mL/min
Phosphorus between 2.5 and 4.5 mg/dL, inclusive
Total corrected (for albumin) serum calcium between 8.5 and 10.5 mg/dL, inclusive
Amylase < 200 U/L
Lipase < 120 U/L
Ability to understand and the willingness to sign a written informed consent document
Agrees to take sevelamer, if indicated, and has no contraindications to use of this medication (that is: known hypersensitivity to sevelamer or component of the formulation; bowel obstruction; active bowel mucosal injury such as ulcerative colitis or gastrointestinal bleeding).
Agrees to follow low phosphate diet, if indicated
Able to swallow and retain oral medication
Women must be postmenopausal, defined as (at least one of):
Women being treated with a LH releasing agonist but who are otherwise of childbearing potential (did not undergo total hysterectomy or bilateral tubal ligation at least 6 weeks before first dose of study drug) must have a negative pregnancy test within 7 days of the first dose of study drug.
Women who are being treated with a LH releasing agonist but are otherwise of childbearing potential must agree to use barrier contraception or an intrauterine device while taking study drug and for 3 months following their last dose of study drug. Alternatively, total abstinence is acceptable if preferred by the subject.
Sexually active men must agree to 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 during this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid.
Exclusion criteria
History of another primary malignancy within 3 years 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.
Neurologic symptoms related to central nervous system metastases requiring increasing doses of corticosteroids. Note that subjects with central nervous system metastases are eligible if they are on a stable corticosteroid dose for at least 2 weeks preceding study entry.
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. Subjects with asymptomatic ophthalmologic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
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 (eg, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
Current evidence of endocrine alterations of calcium/phosphate homeostasis, eg, parathyroid disorders, history of parathyroidectomy, tumor lysis, or tumoral calcinosis.
Currently receiving or planning during study participation to receive treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme inducing anti epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone. See Appendix B for a list of prohibited concomitant medications and supplements.
Has consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges, or products containing juice of these fruits within 7 days prior to first dose of study drug.
Have used amiodarone within 90 days prior to first dose of study drug.
Has used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug. See Appendix B for a list of prohibited concomitant medications and supplements.
Has used calcium or vitamin D within 3 days prior to first dose of study drug. Calcium supplementation may subsequently be used as clinically indicated (for hypocalcemia) on study.
Have clinically significant cardiac disease including any of the following:
Have had a recent (≤ 3 months) transient ischemic attack or stroke.
Pregnant or nursing woman.
Primary purpose
Allocation
Interventional model
Masking
4 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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