A Study of FX-909 in Patients with Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma
- Conditions
- Advanced Solid Tumors CancerOral Drug AdministrationAdvanced Urothelial CarcinomaOpen Label
- Interventions
- Registration Number
- NCT05929235
- Lead Sponsor
- Flare Therapeutics Inc.
- Brief Summary
The goal of this clinical trial is to study the safety and tolerability in all advanced solid tumors, including advanced urothelial carcinoma.
The main question\[s\] it aims to answer are:
* Is FX-909 safe and tolerable
* What is the right dose level for patients
Participants will be asked to take FX-909 daily , in tablet form and record any outcomes from taking the drug. Participants will also be asked to return for multiple site visits for various blood tests and to collect blood and tumor samples as well as have regular CT/MRI scans
- Detailed Description
This is an open-label Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of FX-909 given orally (PO) in patients with advanced solid malignancies. Initially, FX-909 will be given in a dose-escalation phase (Part A) to determine the preliminary recommended phase 2 dose (RP2D). Part B will be a monotherapy expansion phase to further evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of FX-909 in patients with locally advanced (unresectable) and metastatic urothelial carcinoma. Throughout the study patients will be treated in 28-day cycles.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 75
Not provided
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Female patients who are pregnant (confirmed with a positive pregnancy test) or breastfeeding.
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Prior anticancer chemotherapy or small molecule targeted therapy, either investigational or commercially approved and available, within 2 weeks or 5 half-lives (whichever is shorter) prior to the start of study drug administration. When the most recent therapy was a biological therapy (including antibody-drug conjugates), an immune-checkpoint inhibitor (eg, anti-PD(L)1 or anti-CTLA4), or immune agonist, patients should wait 4 weeks before starting therapy with FX-909.
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Prior therapy directly inhibiting PPARG or RXRA.
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Adverse events from prior therapy that have not returned to baseline or stabilized at Grade 1 (except alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade ≤ 2 neuropathy) prior to study drug administration.
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Prior major surgery (excluding placement of vascular access) within 4 weeks before study drug administration.
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Prior radiation therapy with an inadequate washout between the last dose and the start of study drug, defined as follows: 1) at least 2 weeks for palliative radiation to the extremities for osseous bone metastases is required; and 2) at least 4 weeks for radiation to non-extremity sites is required.
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History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free. Exceptions include appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, melanoma in situ status-post full-thickness resection without recurrence, Stage 1 uterine cancer, localized prostate cancer that has been treated surgically with curative intent and presumed cured, or other malignancies with an expected curative outcome.
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QT Interval Corrected Using Fridericia's Formula (QTcF) > 470 msec in screening, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives.
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Known active diagnosis of lipodystrophy/lipoatrophy, or an ongoing need to receive medications known to cause lipodystrophy/lipoatrophy
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Any active uncontrolled systemic bacterial, viral, or fungal infection requiring treatment.
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Known history of human immunodeficiency virus (HIV) seropositivity. Those who have no detectable viral load on highly active antiretroviral therapy (HAART) are permitted.
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Patients with chronic hepatitis B virus (HBV) infection (indicated by a positive HBV surface antigen and/or hepatitis B core antibody). Patietns are permitted with either universal prophylaxis or a pre-emptive treatment approach consistent with regional or national guidelines for patients who receive anticancer therapies.
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Active hepatitis C virus (HCV) infection. Those who have completed curative therapy for HCV and have no detectable viral load are permitted.
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Prior diagnosis of chronic or recurrent (> 1 episode) pancreatitis at any time or a diagnosis of acute pancreatitis within the 6 months prior to screening
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Significant impairment of lung function indicated by resting oxygen saturations below 92% on room air or requiring chronic use of ambulatory supplemental oxygen.
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Uncontrolled or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or carcinomatous meningitis. Asymptomatic brain metastasis is allowed if they have been stable after appropriate radiotherapy for 1 month.
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Need for treatment with high doses of oral or intravenous steroids (> 10 mg/day prednisone or equivalent). Physiologic doses of corticosteroids for treatment of endocrinopathies may be continued if the patient is on a stable dose for at least 1 month.
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Need or anticipated need for treatment with a prohibited therapy described in the protocol during the treatment phase of this study
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Concurrent participation in any other investigational therapeutic study
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History of any of the following cardiovascular diseases:
- Recent history (within the 6 months prior to screening) of serious uncontrolled cardiac arrhythmia (including atrial fibrillation without adequate rate control) or clinically significant ECG abnormalities including second-degree (Type II) or third-degree atrioventricular node block
- Documented cerebrovascular event (stroke or transient ischemic attack), cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the 6 months prior to enrollment
- Congestive heart failure (Class III or IV) as defined by the New York Heart Association functional classification system
- Recent history (within the past 6 months) of symptomatic pericarditis
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Thromboembolic events and/or bleeding disorders ≤ 28 days (eg, deep vein thrombosis or pulmonary embolism) prior to the first dose of study drug
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Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which, in the Investigator's opinion, makes it undesirable for the patient to participate in the study or would jeopardize compliance with the protocol.
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Patients with type 1 diabetes mellitus, or type 2 diabetes mellitus that is not adequately controlled with diet, exercise, or oral hypoglycemic agents and/or injectable agents other than insulin (as defined by HbA1c and fasting plasma glucose criteria in Table 6. Patients taking insulin are excluded from the study. Medication for type 2 diabetes mellitus should have remained stable for the past 14 days prior to screening).
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Known hypersensitivity to FX-909 or any of its excipients (see Table 7 for the list of excipients)
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Patients with gastrointestinal disorders that may interfere with the ability to swallow tablets or absorb study medication
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Patient is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is a member of the study site or Sponsor staff directly involved with this study, unless prospective Institutional Review Board (IRB) or Ethics Committee (EC) approval (by chair or designee) is given allowing exception to this criterion for a specific patient.
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Patients with any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before study entry.
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Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patient's safety or study results.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Expansion Expansion FX-909 When a preliminary RP2D has been identified (this dose may be equal to or below the MTD) evaluate the antitumor activity in locally advanced (unresectable) and metastatic urothelial carcinoma. Dose Escalation FX-909 3+3 design, 5 dose levels,
- Primary Outcome Measures
Name Time Method To assess dose-limiting toxicities, the incidence and severity of adverse events and serious adverse events associated with FX-909 (Safety and Tolerability) through study completion, an average of 3 years Incidence of dose-limiting toxicities (DLTs); Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
- Secondary Outcome Measures
Name Time Method To characterize the pharmacokinetic profile of FX 909 in patients with advanced solid malignancies through study completion, an average of 3 years Plasma pharmacokinetic parameters of FX-909 via percentage of FX-909 in urine
To define the preliminary recommended phase 2 dose of FX-909, and/or maximum tolerated dose (MTD) through study completion, an average of 3 years Assess patients' safety measures (AEs/SAEs) in comparison with patients' objective response rates
To characterize the pharmacokinetic profile of FX-909 in patients with advanced solid malignancies through study completion, an average of 3 years Plasma pharmacokinetic parameters of FX-909 via AUC
To evaluate preliminary antitumor activity of FX 909 in patients with advanced solid malignancies through study completion, an average of 3 years Overall survival (OS)
Trial Locations
- Locations (12)
HonorHealth
🇺🇸Scottsdale, Arizona, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Mass General Cancer Center
🇺🇸Boston, Massachusetts, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Memorial Slone Kettering Cancer Center
🇺🇸New York, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
New Experimental Therapeutics of San Antonio (NEXT)
🇺🇸San Antonio, Texas, United States
South Texas Accelerated Research Therapeutics (START)
🇺🇸San Antonio, Texas, United States