Finding the tolerable recommended dose of KA2507 and how effective it is at treating patient with advance biliary tract cancer who have previously been treated with standard of care chemotherapy

Phase 1

• Conditions: Advanced Biliary Tract Cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001459-38-GB
• Lead Sponsor: Karus Therapeutics Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-10
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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

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) <60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
•Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5 x upper limit of normal (ULN)
-Neutropenia (absolute neutrophil count [ANC]<1.5 x 109/L)
-Platelets <100 x 109/L
-Haemoglobin =9 g/dL). NB the use of transfusion to achieve desired haemoglobin is acceptable
-Total bilirubin =1.5 x ULN (except for patients with known Gilbert’s syndrome)
6.Known haemoglobinopathy due to haemoglobin S or haemoglobin C disease, a or ß thalassemia, or glucose-6-phosphate dehydrogenase deficiency
7.Concomitant use of dapsone
8.Untreated severe thyroid dysfunction (hypo- or hyper-thyroidism)
9.Significant heart disease defined as any of the following:
-New York Heart Association Grade 3 or 4 symptomatic heart failure
-Symptomatic cardiomyopathy
-Unstable angina or acute myocardial infarction within 3 months
-Cardiac ventricular arrhythmia within 3 months that is not controlled by drug therapy and/or by cardiac ablation
-QT interval corrected using Fridericia’s formula (QTcF) >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified