Combination of GNS561 and Trametinib in Patients With Advanced KRAS Mutated Cholangiocarcinoma
ConditionCholangiocarcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGenfit
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed intrahepatic CCA with a documented KRAS mutation.
Patients greater than or equal to 18 years of age.
Patients must have disease progression that is not amenable to potentially curative treatment.
Patients must have received one or two lines of chemotherapy.
Disqualifiers
Previous treatment with a MEK inhibitor or autophagy inhibitor.
Previous treatment with three or more lines of prior chemotherapy.
Extrahepatic CCA with recent (within 6 weeks) placement of a stent or episodes of unstable biliary stents (manifest as obstruction, migration of the stent, infevtion or mechanical failure of the stent) within 6 weeks according to investigator's judgement.
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.
Trial design
Design model
Sequential
Treatments tested in this trial
GNS561 + Trametinib
DrugGNS561: 50mg, 100mg, 150mg, 200mg and trametinib: 1mg, 1.5mg and 2mg
Treatment groups
98 Participants
are divided into 1 treatment groupGroup A: GNS561+TrametinibExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of dose limiting toxicity (DLT) of GNS561 with trametinib (Phase 1b)
Defined as Treatment Emergent Adverse Event (TEAE) being at least possibly related to study drug: With Grade ≥ 3 (using NCI CTCAE Version 5.0 or higher as applicable) such as specified in the protocol
Time frame
At the end of Cycle 1 (each Cycle is 21 days)2
Objective response rate (ORR) of the combination of GNS561 with trametinib (Phase 2a)
Defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time frame
Up to 11 months (estimated)Secondary outcomes
1
Duration of response (DoR)
Defined as the duration between first documentation of CR or PR to first documentation of disease progression or death using RECIST v1.1
Time frame
Up to 11 months (estimated)2
Progression-free survival (PFS)
Defined as the time from the date of first dose of study drug to the date of first documented disease progression or death
Time frame
Up to 11 months (estimated)3
Time To Progression (TTP)
Defined as the time from first dose of study drug to the date of first documented disease progression.
Time frame
Up to 11 months (estimated)4
Disease Control Rate (DCR)
defined as the proportion of patients with a best overall response of CR or PR or stable disease (SD) using RECIST v1.1
Time frame
Up to 11 months (estimated) Source ClinicalTrials.gov