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About
This phase II study evaluates how well pemigatinib works for the treatment of adult patients with pancreatic cancer that has spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started to other places in the body (metastatic) and that have abnormal changes (alterations) in the fibroblast growth factor receptor (FGFR) gene. FGFR genes are genes that, when altered, can lead to and promote the growth of cancer in patients. Researchers want to test if using pemigatinib can block the function of these abnormal FGFR genes and prevent the tumor from growing and whether treatment can help improve overall quality of life.
Full description
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of single agent pemigatinib in patients with advanced or metastatic pancreas cancer of any histologic classification with FGFR2 gene fusions/translocations.
II. To understand response rate and potential for pemigatinib to benefit patients who have other FGFR alterations including point mutations, extracellular small indels and kinase domain duplications in pancreas cancer.
SECONDARY OBJECTIVES:
I. To further evaluate the efficacy of single agent pemigatinib in each above cohort separately.
II. To characterize the safety and tolerability of single agent pemigatinib.
EXPLORATORY OBJECTIVE:
I. To evaluate dynamics of cell-free deoxyribonucleic acid (DNA) (cfDNA) optimized for monitoring response to pemigatinib and detecting emerging resistance mutations to pemigatinib.
OUTLINE: Patients receive pemigatinib orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, computed tomography (CT) and/or magnetic resonance imaging (MRI), and optical coherence tomography (OCT) throughout the study. Patients may also undergo whole body bone scans and dilated fundoscopy as clinically indicated. After completion of study treatment, patients are followed up at 30 days, then every 4 months for one year.
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Inclusion and exclusion criteria
Inclusion Criteria
Patients with histologically or cytologically confirmed advanced or metastatic pancreatic cancer 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 pancreatic cancer 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 pancreas cancer. Patients 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 not eligible for the study
Patients with symptomatic central nervous system (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
Patients ≥ 18 years of age of either gender
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 Incyte)
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
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 , 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, keratoconjuctivitis, 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 pemigatinib (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 pemigatinib 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
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 ≥ 1.5x 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) ≥ 3x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
Alkaline phosphatase ≥ 2.5x 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:
History of clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or arrhythmia requiring therapy. Subjects with a pacemaker and well-controlled rhythm for at least 1 month prior to first dose will be allowed
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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40 participants in 1 patient group
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Central trial contact
The Ohio State University Comprehensive Cancer Center
Data sourced from clinicaltrials.gov
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