Cediranib Versus Placebo Plus Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00939848
• Date of registration: 14/07/2009
• Primary sponsor: University College, London
• Public title: Cediranib Versus Placebo Plus Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers ABC-03
• Scientific title: Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers
• Date of first enrolment: April 2011
• Target sample size: 136
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT00939848
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

United Kingdom

Contacts

• Name: Juan Valle, MD
• Affiliation: Christie Hospital NHS Foundation Trust

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Biliary Tract Neoplasms

Intervention(s)

Drug: cediranib

Drug: cisplatin

Drug: gemcitabine

Drug: Placebo

Primary Outcome(s)

Progression free survival [Time Frame: six months]

Secondary Outcome(s)

• Response Rate (RECIST) • Toxicity • Survival (as part of the follow-on phase III study) • Biomarker evaluation (inc. circulating VEGF, sVEGFR-2, bFGF, LDH and CA 19-9) • Quality of Life [Time Frame: 3 years minimum]

Secondary ID(s)

ABC-03 09/0193

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

AstraZeneca