RECRUITING

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

Conditions

Cholangiocarcinoma GNS561 Trametinib Phase1b/2a

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

Phase 1b/2a Study of GNS561 in Combination with Trametinib in Advanced KRAS Mutated Cholangiocarcinoma

Quick Facts

Study Start:2023-08-21

Study Completion:2026-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05874414

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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).	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.

Inclusion Criteria

Exclusion 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).

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.

Contacts and Locations

Study Contact

Carol ADDY, M.D.

CONTACT

+333 20 16 40 00

clinicaltrial@genfit.com

Carol ADDY, M.D.

CONTACT

866-899-1477

Principal Investigator

Carol ADDY, M.D.

STUDY_DIRECTOR

Genfit

Study Locations (Sites)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

University Of Chicago Medical Center

Chicago, Illinois, 60637

United States

Roswell Park Cancer Institute

Buffalo, New York, 14263

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030

United States

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22908

United States

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Genfit

Carol ADDY, M.D., STUDY_DIRECTOR, Genfit

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-21

Study Completion Date2026-10

Study Record Updates

Study Start Date2023-08-21

Study Completion Date2026-10

Terms related to this study

Keywords Provided by Researchers

GNS561
Cholangiocarcinoma
Trametinib
Phase1b/2a

Additional Relevant MeSH Terms

Cholangiocarcinoma