A Study of Selective HDAC6 Inhibition With KA2507 in Advanced Biliary Tract Cancer

This is an interventional treatment trial for Biliary Tract Cancer Read More

Inclusion Criteria:

• Age ≥18 years
• Signed informed consent
• Histological or cytological diagnosis of advanced (i.e. metastatic disease, or irresectable locally advanced, or recurrent) biliary tract cancer (to include intra or extra hepatic and gall bladder; ampullary cancer will not be included).
• Patient must have disease amenable to biopsy at baseline and consent to pre-treatment biopsy
• Clear evidence of disease progression following standard of care first line therapy with at least 1 measurable lesion using CT/MRI as defined by RECIST 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)
• Previous treatment with any line of chemotherapy for advanced disease (e.g. currently gemcitabine/cisplatin) OR radiotherapy
• ECOG performance status grade 0-1
• Adequate biliary drainage, with no evidence of ongoing infection
• Estimated life expectancy > 3 months
• Patients intolerant of first-line standard of care chemotherapy will also be eligible provided there is evidence of disease progression

Exclusion Criteria:

• Unresolved or unstable serious toxic side-effects of prior chemotherapy or radiotherapy, i.e. ≥ grade 2 per CTCAE (common terminology criteria for adverse events, v5.0) except fatigue, alopecia and infertility
• Clinical evidence of cerebral metastases
• History of previous malignancy that could interfere with response evaluation
• Concurrent treatment with other investigational drugs within 4 weeks of initiating treatment

• Inadequate renal, liver, or haematological function defined as any of:

  • eGFR < 45 ml/min/1.73 m2 using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
  • ALT and/or AST > 5 x ULN
  • Neutropenia (absolute neutrophil count < 1.5 x 109/L)
  • Platelets <100 x 109/L
  • Haemoglobin ≤ 9 g/dL). NB the use of transfusion to achieve desired Hb is acceptable
  • Total bilirubin ≥ 1.5 x ULN (except for patients with known Gilbert's syndrome)
• Known haemoglobinopathy due to HbS or HbC disease, α or β thalassemia, or Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Concomitant use of dapsone
• Untreated severe hypothyroidism

• Significant heart disease defined as any of the following:

  • NYHA grade 3 or 4 symptomatic heart failure
  • 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
  • QTcF > 470 ms on screening ECG or history of Torsades de pointes
• 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
• Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. 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 [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• Active infection requiring antibiotics within two weeks prior to treatment
• Males who are unable to or refuse to use barrier contraception during treatment and for 3 months after
• Women who are pregnant, breast-feeding or either unable to or refuse to use effective means of contraception during treatment
• 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
• 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