GNS561-221-1
| ClinicalTrials.gov Identifier |
| NCT05874414 |
| Institution Name |
| Pan American Center for Oncology Trials, LLC |
| Full Institution Address |
|
Hospital Oncológico Dr. Isaac González Martínez, 150 Av. Centro Médico San Juan Puerto Rico 00935 United States |
| Institution Phone |
| +1 787-407-3333 |
| Institution Website |
| https://panoncologytrials.com |
| Additional Institutions |
|
| Principal Investigator |
| Dr. Marcia Cruz-Correa |
| Principal Investigator Phone |
| +1 (787) 407-3333 |
| Principal Investigator Email |
| info@panoncologytrials.com |
| Additional Principal Investigators |
|
| Study Coordinator |
| Guillermo Pico |
| Study Coordinator Phone |
| (787) 407-3333 |
| Study Coordinator Email |
| guillermo.pico@panoncologytrials.com |
| Additional Study Coordinators |
|
| Study Overview |
|
GNS561 is an inhibitor of autophagy, a protective mechanism that allows tumor cells to be resistant to cancer treatments. Trametinib (“T”) is a drug that blocks the action of proteins that help cancer cells to grow. KRAS mutation in cancer cells may lead to the production of proteins helping cancer cells to grow. “T” might block those proteins, but cancer cells might find another way to grow (autophagy). Adding an inhibitor of autophagy, like GNS561, to “T”, may help to treat patients with CCA with a KRAS mutation. This study [(https://www.clinicaltrials.gov), NCT05874414)] aims to determine the recommended dose of the combination for Phase 2 (RP2DC) and to assess preliminary efficacy/safety of GNS561+”T” in patients with advanced KRAS-mutated CCA. |
| Enrollment Information |
| Up to 74 |
| Study Start Date |
| 20230821 |
| Study End Date |
| 20261031 |
| Study Purpose |
|
Open label, multi-center, Phase 1b/2a study (NCT05874414) Evaluation of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of GNS561+T in adult patients with advanced histologically confirmed KRAS-mutated CCA not amenable to local treatment with surgery or radiotherapy, or with metastatic disease not responding to Standard of Care. Patients are treated in 21-day cycles. Phase 1b (P1b) is conducted in to determine the maximum tolerated doses of GNS561+T. The RP2DC in Phase 2a (P2a) will be based on safety, PK, and PD data from P1b. |
| 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: a) 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. b) Patients who have retinal condition (retinal tear, exudate, hemorrhage) or history of retinal vein occlusion or central serous retinopathy or retinal pigment epithelial detachment. c) History of interstitial lung disease or pneumonitis. d) Patients who have clinically significant pleural effusion or ascites. e) Patients who have neurological condition (e.g., tremor, ataxia, hypotension, confusion), history of seizures or active central nervous system metastases. f) 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). g) 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. h) 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. |
| Required Tests Prior to Study |
|
Before the first study procedure can be done, you will be asked to sign a consent form in duplicate, and you will keep one of the copies. As soon as you have signed the informed consent form, a patient number will be assigned to you for the entire study in order to keep your identity confidential. During this first screening visit, your Study Doctor, or a member of the study team, will perform the following assessments:
If these assessments and procedures show that you can take part in the study, and you choose to take part, you will pursue the screening period and attend the Screening Visit 2 (SV2). If these assessments and procedures show that you cannot continue to the next phase of the study, you will not be enrolled in the study. Screening Visit 2 (SV2) During this visit, your Study Doctor, or a member of the study team, will perform the following assessments:
O Blood samplings for tumor markers will be taken. Patients with your cancer might have raised level(s) of specific tumor marker(s) in their blood. If it is the case, level(s) of your tumor marker(s) will be measured at specific visits (described below). In order to be able to test other specific parameters which could be of interest regarding the exploratory objectives of the study, an additional optional sub-study will be proposed to collect other blood samples and perform other analyses. This biological sample collection and related analyses will only be performed if you have voluntarily given your explicit consent beforehand by signing a dedicated Consent Form. As collection of vital signs is scheduled at the same time as blood samples and ECGs, the order of assessments will be ECGs, vital signs, and blood samples last. If you are a female of childbearing potential, a blood pregnancy test will be performed. You will not be able to take part in the study if you are pregnant or intend to become pregnant or lactating during the study. For this reason, you will have to use a highly effective contraception methods during the study:
A urine sample will be collected. SV2 might be divided into at least 4 visits (a Study Doctor visit, a visit with the cardiologist, a visit with the ophthalmologist and a visit at the imaging facility). For each of these assessments (imaging tests, eye assessment and heart assessment), a dedicated visit will occur with each dedicated health specialists: o Imaging tests – Computed tomography (CT) and/or MRI (Magnetic Resonance Imaging) scans (pelvis, abdomen, chest, and head, and possibly other part(s) of your body according to your Study Doctor judgment) will be performed to identify the areas of cancer in your liver and body. If you have had either of these tests within the last 4 weeks, you may not have to have them again. o Eye examinations to evaluate different eye parameters will be assessed by an eye doctor (ophthalmologist). o Heart assessment either with an echocardiogram or MUGA scan will be performed to check your heart function. Upon receipt of your test results, the Study Doctor will check the criteria for entry into the study. If needed, some blood tests, other procedures, or dedicated visits (for example eye examinations or heart assessment) may need to be repeated to confirm your eligibility [see below paragraph “Retesting screening visit(s)”]. Upon availability of all the results, you will be informed of your eligibility before the first visit of the treatment period. If the result of the tests shows that you cannot continue to the next phase of the study, you will not be included in the study. If you continue in the study, your Study Doctor will schedule the next visit with you. ✓ Retesting screening visit(s): Upon receipt of results from assessments done during the screening phase and in case a retesting or additional testing is needed to confirm your eligibility, additional visit(s) would be scheduled. |
| Potential Side Effects |
|
There is a risk that you could have side effects from the study drugs. GNS561 You may have unwanted effects and symptoms as a result of study treatment with GNS561. The most frequent known and potentially serious unwanted effects and symptoms may include: • gastrointestinal problems. Tell your Study Doctor right away if you have any of the following symptoms:
Metabolism and nutrition disorders : decreased appetite, anorexia
GNS561 may also cause less frequent but potentially serious side effects:
Based on the mechanism of action of GNS561 and the fact that this study drug belongs to a group of drugs called “quinoline derivative”, side effects known for this type of drugs, but not reported for GNS561 so far will be also monitored:
This study includes regular visits with heart assessments including ECGs and echocardiograms to monitor for any potential heart problems that may be related to GNS561. Trametinib You may have unwanted effects and symptoms as a result of study treatment with trametinib. The most frequent known unwanted effects and symptoms may include:
Trametinib may also cause rare but potentially serious side effects:
Tell your Study Doctor right away if you have any of the following symptoms:
blood clots. Trametinib can cause blood clots in your arms or legs, which can travel to your lungs and can lead to death. Get medical help right away if you have the following symptoms:
heart problems, including heart failure. Your Study Doctor should check your heart function before and during treatment with trametinib. Call your Study Doctor and get medical help right away if you have any of the following signs and symptoms of a heart problem:
Tell your Study Doctor if you have any new or worsening symptoms of lung or breathing problems, including:
Tell your Study Doctor right away if you develop any of the following signs or symptoms of a severe skin reaction, including:
Before you take trametinib, please inform your Study Doctor about all your medical conditions, including if you:
Your Study Doctor will take all appropriate measures in case of any adverse event to ensure your safety until the return to normal or until stability of your condition. This may imply that safety follow-up may continue after you have left the study and that additional investigations may be requested by your Study Doctor or by the Sponsor, notably for potential related adverse events. Certain markers in your blood and urine that may suggest metabolic, liver, muscle, heart or kidney problems may also be affected by study drugs. All these parameters will be closely monitored during the study. As GNS561 is an experimental drug in development, it is possible that there may be unknown side effects. For trametinib, these side effects mentioned above are not all the possible side effects. If you suffer from any symptoms during the study (whether you believe it is related to the study drug or not, and whether or not it is listed above), you have to report them to your Study Doctor, even if it is not during the scheduled visit. |
| Financial Assistance Available |
| Yes |