ABC-08: Phase Ib Trial of Acelarin in Combination With Cisplatin in Locally Advanced/ Metastatic Biliary Tract Cancers

Inclusion Criteria:

* Histologically/cytologically verified, non-resectable or recurrent/metastatic cholangiocarcinoma, gallbladder or ampullary carcinoma.
* No prior systemic therapy allowed for advanced biliary cancer. Prior low dose chemotherapy used with or without radiotherapy in the adjuvant setting is allowed if completed \> 6 months from enrolment. Recent palliative radiation (within 28 days prior to consent) is allowed if candidate has measurable disease outside radiation field.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Age ≥ 18 years and life expectancy \> 3 months.
* Adequate renal function with serum urea and serum creatinine \< 1.5 times upper limit of normal (ULN) and creatinine clearance ≥ 30ml/min.
* Adequate haematological function: Hb ≥ 10g/dl, white blood count (WBC) ≥ 3.0 x 10\*9/L, absolute neutrophil count (ANC) ≥ 1.5 x 10\*9/L, platelet count ≥ 100,000/mm3.
* Adequate liver function: total bilirubin \< 30 μmol/L and alkaline phosphatase, along with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 5 x ULN.
* Adequate biliary drainage, with no evidence of ongoing infection.
* Women of child bearing age MUST have a negative pregnancy test prior to study entry AND be using a highly effective contraception method (combined or progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, vasectomised partner\*(a) or sexual abstinence\*\*(b)) which must be continued for 6 months after the end of study treatment, unless child bearing potential has been terminated by surgery/radical radiotherapy or infertility due to bilateral tubal occlusion.
* Male subjects must either have had a successful vasectomy (confirmed azoospermia) or they and their female partner meet the criteria above (not of childbearing potential or practicing adequate contraception \[e.g. combined or progestogen-only hormonal contraception, intrauterine device, intrauterine hormone-releasing system, sexual abstinence\*\*(b)\] throughout the study period and for 6 months after the end of study treatment).
* Patients must not have a history of other malignant diseases (within the previous 5 years and there must be no evidence of recurrence), other than adequately treated non-melanotic skin cancer or in-situ carcinoma of the uterine cervix.
* Patients must have given written informed consent.

  * (a) The vasectomised partner must have received medical assessment confirming surgical success.

    * (b) Sexual abstinence in line with the preferred and usual lifestyle of the subject.

Exclusion Criteria:

* History of allergic reactions attributed to previous gemcitabine or cisplatin treatment.
* Documented history of allergic reactions attributed to any of the excipients used in the formulation (Kolliphor ELP; Tween 80; DMA).
* Previous treatment with Acelarin.
* Incomplete recovery from previous therapy (surgery/adjuvant therapy/radiotherapy) or unresolved biliary tree obstruction.
* Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the trial.
* Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the trial.
* Any patient with a medical or psychiatric condition that impairs their ability to give informed consent.
* Any other serious uncontrolled medical conditions.
* Clinical evidence of metastatic disease to the brain.
* Any pregnant or lactating woman.
* Pre-existing hearing impairment.