Trial Title:
Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutation Cholangiocarcinoma
NCT ID:
NCT05874414
Condition:
Cholangiocarcinoma
Conditions: Official terms:
Cholangiocarcinoma
Trametinib
Conditions: Keywords:
GNS561
Cholangiocarcinoma
Trametinib
Phase1b/2a
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GNS561 + Trametinib
Description:
GNS561: 50mg, 100mg, 150mg, 200mg and trametinib: 1mg, 1.5mg and 2mg
Arm group label:
GNS561+Trametinib
Other name:
Ezurpimtrostat (GNS561)
Summary:
This is an open-label, multicenter Phase 1b/2a study to evaluate safety, pharmacokinetics
(PK), pharmacodynamics (PD) and efficacy of GNS561 in combination with trametinib in
Advanced KRAS Mutated Cholangiocarcinoma after failure of standard-of-care first line
therapy
Criteria for eligibility:
Criteria:
Inclusion criteria:
1. Histologically confirmed CCA with a documented KRAS mutation.
2. Patients greater than or equal to 18 years of age.
3. Patients must have disease progression that is not amenable to potentially curative
treatment.
4. Patients must have received at least one line of chemotherapy.
5. Patients must have at least one measurable disease by RECIST v1.1.
6. Performance status (ECOG) 0-1.
7. Adequate organ baseline function defined as follows: absolute neutrophil count ≥1500
cells/μL, platelet count ≥100,000 cells/μL, hemoglobin ≥9 g/dL, aspartate
aminotransferase or alanine aminotransferase less than or equal to 5 × upper limit
of normal, estimated glomerular filtration rate ≥60 mL/min, corrected QT interval by
Fridericia's (QTcF) interval ≤470 msec.
8. Women of childbearing potential must present with a negative serum pregnancy test
and agree to use adequate contraception during the study and until 6 months after
the end of treatment. Male patients with women partners of childbearing potential
must agree with the contraception procedures of the study protocol.
9. Patients must be able to understand and be willing to comply with the requirements
of the study protocol.
10. Patients participate voluntarily and sign informed consent form(s).
Exclusion criteria:
1. Previous treatment with a MEK inhibitor or autophagy inhibitor.
2. Current evidence of uncontrolled, significant intercurrent illness including, but
not limited to, the following conditions:
1. Cardiovascular disorders: congestive heart failure New York Heart Association ≥
class 2 or left ventricular ejection fraction (LVEF) <50%, arrythmias or
cardiac conduction abnormalities, history of coronary disease (including
myocardial infarction, unstable angina), history of angioplasty or stenting
within 6 months prior to enrollment.
2. Patients who have retinal condition (retinal tear, exudate, hemorrhage) or
history of retinal vein occlusion or central serous retinopathy or retinal
pigment epithelial detachment.
3. History of interstitial lung disease or pneumonitis.
4. Patients who have clinically significant pleural effusion or ascites.
5. Patients who have neurological condition (e.g., tremor, ataxia, hypotension,
confusion), history of seizures or active central nervous system metastases.
6. Impairment of gastrointestinal function or gastrointestinal disease (e.g.,
diarrhea, active ulcer disease, history of gastrointestinal
perforation/hemorrhage, malabsorption or other conditions that under the
judgment of the principal investigator (PI) may impair absorption of study
drugs).
7. Patients who are taking antineoplastic drugs for concomitant cancer or history
of another malignancy with the exception of patients who have been disease-free
for at least 3 years.
8. Any other condition that would, in the Investigator s judgment, contraindicate
the patients' participation in the clinical study due to safety concerns or
compliance with clinical study procedures (e.g., infection, unable to swallow
medication, social/psychological issues, etc).
3. Known clinically significant liver disease, including alcoholism, cirrhosis, fatty
liver, or inherited liver disease as well as active viral disease including HBV and
HCV.
4. Patients with known allergic reaction to quinoline derivatives (e.g., quinine,
chloroquine, mefloquine) and/or hypersensitivity to study drugs.
5. Female patients who are pregnant or lactating at the time of enrollment.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
USC Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
USC Norris Comprehensive Cancer Center
Facility:
Name:
University Of Chicago Medical Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
University Of Chicago Medical Center
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Roswell Park Cancer Institute
Facility:
Name:
Hospital of the University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Perelman Center for Advanced Medicine
Facility:
Name:
University of Texas, MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
The University of Texas, MD Anderson Cancer Center
Facility:
Name:
University of Virginia Comprehensive Cancer Center
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Status:
Recruiting
Contact:
Last name:
University of Virginia Health System
Facility:
Name:
Froedtert Hospital and the Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Contact:
Last name:
Medical College of Wisconsin
Facility:
Name:
Pan American Center for Oncology Trials, LLC
Address:
City:
Rio Piedras
Zip:
00935
Country:
Puerto Rico
Status:
Recruiting
Contact:
Last name:
Pan American Center for Oncology Trials, LLC
Start date:
August 21, 2023
Completion date:
October 2026
Lead sponsor:
Agency:
Genfit
Agency class:
Industry
Source:
Genfit
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05874414
