Trial Title:
A Study of FX-909 in Patients With Advanced Solid Malignancies, Including Advanced Urothelial Carcinoma
NCT ID:
NCT05929235
Condition:
Advanced Solid Tumors Cancer
Advanced Urothelial Carcinoma
Oral Drug Administration
Open Label
Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
3+3 dose escalation design with 1 expansion arm at RP2D
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
FX-909
Description:
FX-909 is an orally available new molecular entity that inhibits basal- and
ligand-activated transcription by PPARG.
Arm group label:
Dose Escalation
Arm group label:
Expansion Expansion
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.
Criteria for eligibility:
Criteria:
1. Able to understand and willing to sign an informed consent.
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
4. Part A (Dose Escalation): Histologically or cytologically diagnosed, locally
advanced (unresectable) or metastatic solid malignancies that have progressed after
all available standard therapy for the specific tumor type, or for which no standard
therapy exists. Patients for whom standard therapies are intolerable or considered
inappropriate by the Investigator are eligible.
Part B (Expansion): Histologically or cytologically diagnosed, locally advanced
(unresectable) or metastatic urothelial carcinoma with defined genetic alterations.
Patients in Part B must have progressed after all available standard therapy (eg,
anti- programmed cell death (ligand) 1 [PD(L)1], antibody-drug conjugate[s], and
platinum-based doublet chemotherapy), been unable to tolerate standard therapy, or
be considered inappropriate for standard therapy by the Investigator.
5. Part A (Dose Escalation): Patients with or without measurable disease (as defined by
RECIST version 1.1) will be eligible for enrollment.
Part B (Expansion): Patients must have measurable disease per RECIST version 1.1
with ≥ 1 site of measurable disease that has not been previously irradiated or has
progressed after radiation therapy.
6. An archival, paraffin-embedded, formalin-fixed, tumor sample (see Laboratory Manual
for details) that is no more than 30 months old at the time of screening. If an
archival tumor sample is not available or is older than 30 months, then the patient
must consent to provide a fresh biopsy during screening.
7. Screening laboratory values meet the criteria outlined in the protocol. Hematologic
criteria may be met with transfusion of blood products or administration of G-CSF,
provided they are not given within 7 days of C1D1.
Exclusion Criteria:
1. Female patients who are pregnant (confirmed with a positive pregnancy test) or
breastfeeding.
2. 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.
3. Prior therapy directly inhibiting PPARG or RXRA.
4. 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.
5. Prior major surgery (excluding placement of vascular access) within 4 weeks before
study drug administration.
6. 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.
7. 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.
8. 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.
9. Known active diagnosis of lipodystrophy/lipoatrophy, or an ongoing need to receive
medications known to cause lipodystrophy/lipoatrophy
10. Any active uncontrolled systemic bacterial, viral, or fungal infection requiring
treatment.
11. Known history of human immunodeficiency virus (HIV) seropositivity. Those who have
no detectable viral load on highly active antiretroviral therapy (HAART) are
permitted.
12. 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.
13. Active hepatitis C virus (HCV) infection. Those who have completed curative therapy
for HCV and have no detectable viral load are permitted.
14. 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
15. Significant impairment of lung function indicated by resting oxygen saturations
below 92% on room air or requiring chronic use of ambulatory supplemental oxygen.
16. 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.
17. 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.
18. Need or anticipated need for treatment with a prohibited therapy described in the
protocol during the treatment phase of this study
19. Concurrent participation in any other investigational therapeutic study
20. 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
21. Thromboembolic events and/or bleeding disorders ≤ 28 days (eg, deep vein thrombosis
or pulmonary embolism) prior to the first dose of study drug
22. 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.
23. 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).
24. Known hypersensitivity to FX-909 or any of its excipients (see Table 7 for the list
of excipients)
25. Patients with gastrointestinal disorders that may interfere with the ability to
swallow tablets or absorb study medication
26. 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.
27. 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.
28. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
HonorHealth
Address:
City:
Scottsdale
Zip:
85258
Country:
United States
Status:
Recruiting
Contact:
Last name:
HonorHealth Nurse Navigation Team
Phone:
480-323-1791
Contact backup:
Phone:
833-354-6667
Investigator:
Last name:
Sunil Sharma, MD
Email:
Principal Investigator
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06519
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amanda Davis, LPN
Phone:
475-321-7899
Email:
Amanda.Davis@yale.edu
Investigator:
Last name:
Daniel Petrylak, MD
Email:
Principal Investigator
Facility:
Name:
Mass General Cancer Center
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xin Gao, MD
Phone:
617-724-4000
Email:
xgao4@mgb.org
Investigator:
Last name:
Xin Gao, MD
Email:
Principal Investigator
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brian Rasp
Phone:
857-215-2265
Email:
Brian_Rasp@DFCI.Harvard.edu
Investigator:
Last name:
Charlene Mantia, MD, Ph.D.
Email:
Principal Investigator
Facility:
Name:
Icahn School of Medicine at Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lindsay Diamond
Phone:
347-514-1561
Email:
lindsay.diamond@mssm.edu
Contact backup:
Last name:
Erin Heath
Phone:
646-901-3172
Email:
erin.heath@mssm.edu
Investigator:
Last name:
Matthew Galsky, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Slone Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Gopakumar V Iyer, MD
Phone:
646-888-4737
Email:
iyerg@mskcc.org
Investigator:
Last name:
Gopa Iyer, MD
Email:
Principal Investigator
Facility:
Name:
UNC Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27514
Country:
United States
Status:
Recruiting
Contact:
Phone:
877-668-0683
Email:
cancerclinicaltrials@med.unc.edu
Investigator:
Last name:
Matthew Milowsky, MD
Email:
Principal Investigator
Facility:
Name:
The Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Contact:
Last name:
Cancer Answer
Phone:
216-444-7923
Email:
canceranswer@ccf.org
Investigator:
Last name:
Shilpa Gupta, MD
Email:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
askSARAH
Phone:
844-482-4812
Investigator:
Last name:
Benjamin Garmezy, MD
Email:
Principal Investigator
Facility:
Name:
New Experimental Therapeutics of San Antonio (NEXT)
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brianna Flores, BSN, RN
Phone:
210-580-9521
Email:
bflores@nextoncology.com
Investigator:
Last name:
Ildefonso Ismael Rodriguez Rivera, MD
Email:
Principal Investigator
Facility:
Name:
South Texas Accelerated Research Therapeutics (START)
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Contact:
Last name:
Angela Galindo
Email:
angela.galindo@thestartcenter.com
Contact backup:
Last name:
Jessie Fernandez
Email:
jessie.fernandez@startsa.com
Investigator:
Last name:
Drew Rasco, MD
Email:
Principal Investigator
Start date:
August 24, 2023
Completion date:
January 30, 2027
Lead sponsor:
Agency:
Flare Therapeutics Inc.
Agency class:
Industry
Source:
Flare Therapeutics Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05929235
