Clinical trial testing the drug cediranib(AZD2171)against placebo with cisplatin / gemcitabine chemotherapy for patients with advanced biliary tract cancers

Phase 1

• Conditions: MedDRA version: 17.0 Level: LLT Classification code 10017617 Term: Gallbladder cancer non-resectable System Organ Class: 100000004864; biliary tract carcinomas (including gallbladder cancer and cholangiocarcinomas); MedDRA version: 17.0 Level: LLT Classification code 10004595 Term: Bile duct cancer NOS System Organ Class: 100000004864; MedDRA version: 17.0 Level: LLT Classification code 10008594 Term: Cholangiocarcinoma non-resectable System Organ Class: 100000004864

• Registration Number: EUCTR2009-013408-30-GB
• Lead Sponsor: niversity College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-07-06
• Study Completion: 2014-09-29
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 124

Inclusion Criteria

• A histopathological/cytological diagnosis of non-resectable or recurrent/metastatic biliary tract carcinoma (intra- or extra-hepatic), gallbladder or ampullary carcinoma
• ECOG performance status 0, or 1
• Age = 18
• Estimated life expectancy > 3 months
•Adequate haematological function:
o Haemoglobin = 10g/dl*
o White blood cell count (WBC) = 3.0 x 10*9/L
o absolute neutrophil count (ANC) = 1.5 x 10*9/L
o Platelet count = 10*9/L
*prior transfusions for patients with low haemoglobin are allowed
• Adequate liver function:
o Total bilirubin =1.5 x upper limit of normal (ULN) (except for patients with known documented cases of Gilbert’s syndrome)
o ALT and/or AST = 5.0 x ULN (If liver metastases are present, ALT or AST < 5 x ULN)
o alkaline phosphatase = 5 x ULN
• Adequate renal function:
o serum urea < 1.5 x ULN
o serum creatinine < 1.5 x ULN
o calculated GFR = 45ml/min. If the calculated GFR is below 45, isotope EDTA confirmation of adequate renal function is required
• 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 must 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
• Patient must have given written informed consent

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 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

• Significant haemorrhage (>30ml bleeding/episode in previous 3 months) or haemoptysis (>5 ml fresh blood) within 4 weeks of randomisation
• 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 (CTCAE grade >1) from previous anti-cancer therapy (except haematological toxicity – see inclusion criteria for adequate haematological function), or alopecia
• 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 (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 <1.5g in a 24-hour period or protein/creatinine ratio < 1.5
• History of significant gastrointestinal impairment, as judged by the Principal Investigator that would significantly affect the absorption of cediranib
• Mean QTc with Bazetts correction >480 msec in screening ECG or history of familial long QT syndrome
• Recent (<14 days) major thoracic or abdominal surgery prior to randomisation, or a surgical incision that is not fully healed
• Pregnant or breast-feeding women
• Known hypersensitivity to cediranib or any of its excipients
• Known risk of the patient transmitting HIV, hepatitis B or C via infected blood
• Treatment with an investigational drug within 30 days prior to randomisation
• Other concomitant anti-cancer therapy (except steroids)
• 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 psychiatric or other disorder (eg symptomatic brain metastases) likely to impact on informed consent
• N.B. Whilst not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and, in those randomised to cisplatin, should be followed by repeat audiograms prior to cycle 2

Study & Design

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