Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutated Cholangiocarcinoma

Launched by GENFIT · May 22, 2023

Keywords

ClinConnect Summary

This clinical trial is studying the safety and effectiveness of a combination of two medications, GNS561 and trametinib, in treating advanced cholangiocarcinoma (a type of cancer affecting the bile ducts) in patients who have a specific gene mutation called KRAS. This study is aimed at patients who have already tried standard treatments but their cancer has continued to progress. The trial is open to adults aged 18 and older, who have a confirmed diagnosis of cholangiocarcinoma with a KRAS mutation, and who have measurable disease that can be assessed during the trial.

Participants in this trial can expect to receive the combination of these two drugs, which may help slow down or stop the growth of their cancer. Before joining, patients will need to meet certain health criteria to ensure their safety during the study. Those interested in participating should be ready to sign a consent form and agree to follow the study guidelines. It’s important for patients to discuss with their doctors if they are eligible and how this trial might fit into their treatment plan.

Gender

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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 ≥1000 cells/μL, platelet count ≥75,000 cells/μL, hemoglobin ≥9 g/dL, aspartate aminotransferase or alanine aminotransferase less than or equal to 3 × 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. Uncontrolled arterial hypertension or inadequately controlled arterial hypertension, at the discretion of the investigator, based on an average of = \>3 BP readings over = \>2 sessions.
• • 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 malignancy other than CCA within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%) such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
• • 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 active viral hepatitis, 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.