Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers
Brief Summary: As a result of our previous NCRN study (ABC-02) cisplatin and gemcitabine (CisGem) is likely to become the international standard of care for patients with advanced biliary tract cancer (submitted: ASCO 2009).

This study, ABC-03, will determine whether the addition of cediranib(an oral Vascular Endothelial Growth Factor Receptor inhibitor) to CisGem will improve the time to disease progression in this patient group.


Options:
A: Inclusion Criteria:

* Histologically or cytologically-confirmed advanced (unresectable or metastatic) biliary tract cancer (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma)
* Patients must have measurable or evaluable but non-measurable disease
* Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted).
* WHO performance status 0 to 2: patients must have a WHO PS ≤ 2

Exclusion Criteria:

* Patients must not have received prior systemic therapy for advanced (unresectable or metastatic) disease; prior chemotherapy in the adjuvant setting within 3 months before the trial entry is accepted
* Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance wit
* Significant cardiovascular event (e.g. myocardial infarction, superior vena cava \[SVC\] syndrome, New York Heart Association \[NYHA\] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of
* History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG
B: Inclusion Criteria:

* A histopathological/cytological diagnosis of non-resectable or recurrent/metastatic biliary tract carcinoma (intra- or extra-hepatic), gallbladder or ampullary carcinoma
* Measurable disease on CT or MR scanning. Radiological assessments must be done within 4 weeks of randomisation
* ECOG performance status 0 or 1
* Age ≥ 18 and estimated life expectancy \> 3 months
* Adequate haematological function: Haemoglobin ≥ 10g/dl\*; WBC ≥ 3.0 x 109/L; Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelet count ≥ x 109/L, \*prior transfusions for patients with low haemoglobin are allowed
* Adequate liver function : Total bilirubin ≤1.5 x upper limit of normal (ULN); ALT and/or AST ≤ 2.5 x ULN (If liver metastases are present, ALT or AST \< 5 x ULN)
* Alkaline phosphatase ≤ 5 x ULN
* Adequate renal function with serum urea and serum creatinine \< 1.5 times ULN and a calculated GFR ≥ 45 mL/min. If the calculated GFR is below 45 mL/min, isotope EDTA confirmation of adequate renal function is required
* Adequate biliary drainage, with no evidence of active uncontrolled infection (patients on long-term antibiotics are eligible provided signs of active infection have resolved)
* Women of child-bearing potential should have a negative pregnancy test prior to study entry AND be using an adequate contraception method, which must be continued for 3 months after completion of chemotherapy

Exclusion Criteria:

* Significant haemorrhage (\>30 mL bleeding/episode in previous 3 months) or haemoptysis (\>5 mL fresh blood in previous 4 weeks)
* Patients with history of poorly controlled hypertension with resting blood pressure \>150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy, or patients who are requiring maximal doses of calcium channel blockers to stabilise blood pressure
* Incomplete recovery (grade CTC \>1) from previous anti-cancer therapy (except haematological toxicity - see eligibility for adequate haematological function, or alopecia) or unresolved biliary tree obstruction
* Prior therapy with chemoradiotherapy (either adjuvant or in the locally advanced setting)
* 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 (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
* Untreated unstable brain or meningeal metastases. Patients with radiological evidence of stable brain metastases are eligible providing that they are asymptomatic and either do not require corticosteroids or have been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids
* Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein \<1.5 g in a 24-hour period
* History of significant gastrointestinal impairment, as judged by the Investigator, that would significantly affect the absorption of cediranib
* Mean QTc with Bazetts correction \>470 msec in screening ECG or history of familial long QT syndrome
* Recent (\<14 days) major thoracic or abdominal surgery prior to entry into the study, or a surgical incision that is not fully healed
* Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication
* Known hypersensitivity to cediranib or any of its excipients
* Known risk of the patient transmitting HIV, hepatitis B or C via infected blood
* Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site(s)
* Previous enrolment or randomisation of treatment in the present study
* Treatment with an investigational (non-registered) drug within 30 days prior to the first dose of cediranib
* Other concomitant anti-cancer therapy (except steroids)
* Incomplete recovery from previous surgery or unresolved biliary tract obstruction
* Patients undergoing current treatment with curative intent
* History of prior malignancy that will interfere with the response evaluation (exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, any early stage (stage I) malignancy adequately resected for cure greater than 5 years previously)
* Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
* Any psychiatric or other disorder (eg brain metastases) likely to impact on informed consent
* NB. Whilst not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, it is recommended that audiograms be carried out at baseline and prior to cycle 2.
C: Inclusion criteria:

* Cyto-/histological confirmed unresectable, locally advanced, or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma or adenocarcinoma of gallbladder, but NOT other peri-ampulla Vateri or mixed tumor.
* At least one, not previously irradiated, measurable lesion according to RECIST (version 1.1).
* Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
* Aged no less than 20 years, at the time of acquisition of informed consent.
* Life expectancy \>= 3 months.
* Adequate organ and bone marrow function as defined below: WBC \>= 3.00 × 103/L and absolute neutrophil count \>= 1.50 × 103/L, Platelet count \>= 100 × 103/L, Hemoglobin level \>= 10 g/dL, Serum creatinine \<= 1.5 x Upper Normal Limit (UNL) and calculated GFR \>= 40mL/min, Serum bilirubin \<= 1.5 x UNL , ALT \<= 2.5x UNL.
* Ability to understand and willingness to sign written Informed Consent Form.

Exclusion criteria:

* Other anti-tumor agent such as systemic chemotherapy, immunotherapy or EGFR/VEGF-pathway-targeting therapy before the commencement of study treatment.
* Radiotherapy (except palliative irradiation of bone lesions) within 4 weeks before the commencement of study treatment.
* Other cancer or prior treatment for other carcinomas within the last five years, except cured non-melanoma skin cancer and treated in-situ cervical cancer.
* Known CNS metastasis.
* Major surgery within 4 weeks prior to start of study treatment (diagnostic biopsy, laparotomy, line placement is not considered as major surgery).
* Pre-existing peripheral neuropathy \>= grade 2.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in the past 12 months, active gastrointestinal bleeding, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator.
* Having received any investigational agents or participated in any investigational drug study within 4 weeks prior to study enrollment.
* Pregnant or breast-feeding female (a pregnancy test must be performed on all female patients who are of child-bearing potential before entering the study, and the result must be negative).
* Poor compliance.
D: Inclusion Criteria:

1. Pathologically proven biliary adenocarinoma
2. Age \> 18
3. Evaluable disease
4. ECOG performance status of 2 or better
5. No prior exposure to chemotherapy, but adjuvant chemotherapy (or chemoradiotherapy) completed 6 moths or more before study enrollment is allowed
6. Adequate bone marrow function A. WBCs \> 4,000/µL, absolute neutrophil count \[ANC\]\>1,500/µL B. Hemoglobin \>9.0 g/dL C. Platelets \> 100,000/µL
7. Adequate kidney function (creatinine\<1.5 mg/dL)
8. Adequate liver function (bilirubin\<1.5 mg/dL \[\< 2.5 mg/dL for obstructive jaundice with adequately decompressed bile duct obstruction\], transaminases levels\<3 times the upper normal limit, and serum albumin of \>2.5 mg/dL)
9. No serious medical or psychological condition that would preclude study treatment
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

1. Other tumor type than adenocarcinoma
2. Evidence of GI bleeding or GI obstruction
3. Presence or history of CNS metastasis
4. Pregnancy or breastfeeding
5. Other serious illness or medical conditions
6. Axial skeletal radiotherapy within 6 months
7. Neuropathy grade 2 or worse

Answer: B