Advanced Biliary Tract Cancer
Conditions
Interventions
Product Name: KA2507
Product Code: N/A
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: KA2507
CAS Number: N/A
Current Sponsor code: KA2507
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Karus Therapeutics Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years 2. Signed informed consent 3. Histological or cytological diagnosis of advanced (i.e. metastatic disease, or irresectable locally advanced, or recurrent) BTC (to include intra or extra hepatic and gallbladder; ampullary cancer will not be included) 4. Patient must have disease amenable to biopsy and be willing to undergo this procedure at baseline and on-treatment 5. Clear evidence of disease progression following standard of care first line therapy as defined by RECIST Version 1.1, OR clear evidence of disease progression based on the emergence of non-measurable disease (e.g. new cytologically confirmed ascites, pleural or pericardial effusion). Patients intolerant of first-line standard of care chemotherapy will also be eligible provided there is evidence of disease progression 6. At least one target lesion measurable as defined by RECIST Version 1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) 7. Eastern Co-operative Ongology Group (ECOG) performance status Grade 0 or 8. Adequate biliary drainage, with no evidence of ongoing infection 9. Estimated life expectancy >3 months Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. Unresolved or unstable adverse effects of prior chemotherapy or radiotherapy, i.e. =Grade 2 according to CTCAE Version 5.0 except alopecia and infertility 2. Clinical evidence of cerebral metastases 3. History of previous malignancy that could interfere with response evaluation 4. Concurrent treatment with other investigational drugs within 4 weeks or 6 half-lives of initiating treatment 5. Inadequate renal, liver, or haematological function defined as any of: • Significant renal impairment, defined as estimated glomerular filtration rate (eGFR) 5 x upper limit of normal (ULN) - Neutropenia (absolute neutrophil count [ANC]470 ms on screening ECG or history of Torsades de pointes 10. Any other concurrent severe and/or uncontrolled medical or surgical condition which, in the view of the Investigator, could compromise the patient’s participation in the study 11. Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C virus (HCV). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid 12. Active infection requiring antibiotics within two weeks prior to treatment 13. Males who are unable or unwilling to use barrier contraception during treatment and for 3 months after 14. Women who are pregnant, breast-feeding or either unable or unwilling to use effective means of contraception during treatment 15. Patients who are unable to swallow capsules and/or have a surgical or anatomical condition that precludes swallowing and absorbing oral medication on an ongoing basis 16. Any other condition that would, in the Investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the preliminary efficacy of KA2507 in patients with advanced biliary tract cancer previously treated with standard of care chemotherapy ;Secondary Objective: To evaluate tumour response to KA2507 (response rates and duration of response) To evaluate overall survival To characterise the safety and tolerability profile of KA2507. To characterise the pharmacokinetic profile of KA2507 in a subset of patients To determine the pharmacodynamic response to KA2507 in a subset of patients ;Primary end point(s): To assess the preliminary efficacy of KA2507 in patients with advanced biliary tract cancer previously treated with standard of care chemotherapy. This will will be measured by Progression free survival (PFS) at 4 months (objective disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1. ;Timepoint(s) of evaluation of this end point: Reports will be provided by the TMG to the Independent Data Monitoring Committee (IDMC), who will review accrual, compliance, safety and efficacy. The first review will be triggered after the first six patients have completed 4 months of follow-up. The second review by the IDMC will be triggered after 17 patients are treated once 4-month PFS data are available for these 17 patients, and at least once each year thereafter. If less than 3 patients out of the first 17 are alive and progression-free at 4 months the IDMC might recommend the stop the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To assess the effect of KA2507 on overall response rate, duration of objective response, duration of disease control and time to progression per RECIST Version 1.1. • Overall survival - Time to death after study treatment. • Incidence of adverse events (CTCAE Version 5.0), clinical laboratory abnormalities and 12-lead ECG abnormalities to characterise the safety and tolerability profile of KA2507 at the recommended phase II dose. • Worst grade of adverse events (CTCAE Version 5.0)to characterise the safety and tolerability profile of KA2507 at the recommended phase II dose. • Frequency of dose modifications, discontinuations, dose interruptions to characterise the safety and tolerability profile of KA2507 at the recommended phase II dose. • KA2507 plasma pharmacokinetic parameters including Tmax, Cmax, T½, AUC0-t, AUClast and AUC0-8 to characterise the pharmacokinetic profile of KA2507 at the RP2D for up to 6 patient. • To determine the pharmacodynamic response to KA2507 for up to 6 patients. ;Timepoint(s) of evaluation of this end point: The best ORR consists of the best among all objective responses assessed. OS is defined as the time from registration to death from any cause. PFS is defined as time from registration to time of progression or time of death from any cause. Duration of objective response is defined as the time from initial complete or partial response to disease progression or death on study from any cause whichever occurs first. Duration of disease control is defined as the time from start of treatment to disease progression | — |
Countries
United Kingdom
Contacts
Public ContactMichelle Hung
Cancer Research UK & Cancer Trials Centre
Outcome results
None listed