Cediranib Versus Placebo Plus Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers (ABC-03)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
University College, London
ClinicalTrials.gov Identifier:
NCT00939848
First received: July 14, 2009
Last updated: October 8, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Biliary Tract Neoplasms
Drug: gemcitabine
Drug: cisplatin
Drug: Placebo
Drug: cediranib
Phase 2
Phase 3

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
Official Title: Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: six months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 136
Study Start Date: April 2011
Estimated Study Completion Date: September 2014
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B
The experimental arm will consist of cisplatin 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle with cediranib 20mg oral daily (continuous dosing).
Drug: cisplatin
cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
Drug: cediranib
cediranib 20mg oral daily (continuous dosing)until evidence of disease progression has been confirmed
Other Name: AZD2171
Drug: gemcitabine
gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
Placebo Comparator: Arm A
The control arm will consist of cisplatin 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle with a matching placebo 20mg oral daily (continuous dosing)
Drug: gemcitabine
gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
Drug: cisplatin
cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
Drug: Placebo
20mg od (continuous dosing) until evidence of disease progression has been confirmed

Detailed Description:

Although there is currently no standard chemotherapy for patients with advanced biliary tract cancers (ABC) the UK ABC-02 study (the largest study by far in this patient group, n=410) is likely to define CisGem as the global standard of care for this disease based on a significantly improved progression-free survival and overall survival compared to gemcitabine alone.

Vascular endothelial growth factor (VEGF) is a pivotal stimulus of physiologic and pathologic angiogenesis, including the sustained neo-vascularisation required to support solid tumour growth. Human biliary tract carcinoma cells have higher expression of VEGF both in cell lines and tissues (detected in 75.6% of 33 resected clinical specimens) and this is associated with significantly higher levels of microvessel density and the presence of intrahepatic metastases.

Cediranib is a highly potent inhibitor of VEGF receptor 2 tyrosine kinase and VEGF-induced signalling in endothelial cells. It has been safely combined with a CisGem regimen in lung cancer patients.

Aims This trial aims to evaluate the effect on progression-free survival of cediranib in combination with CisGem chemotherapy compared to CisGem and placebo.

Summary of study Consenting patients with ABC (inoperable, locally advanced, recurrent or metastatic) will receive CisGem chemotherapy and either cediranib (experimental arm) or placebo (standard arm) orally. Treatment will continue until disease progression (chemotherapy will stop at 24 weeks) with tumour reassessment by CT/MRI scans at 12-weekly intervals. All patients will be followed up for survival analysis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00939848

Locations
United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom, NW1 2PQ
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
University College, London
AstraZeneca
Investigators
Principal Investigator: Juan Valle, MD Christie Hospital NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Director of Research Support, University College London (Joint UCLH & UCL Biomedical Research Unit)
ClinicalTrials.gov Identifier: NCT00939848     History of Changes
Other Study ID Numbers: ABC-03 09/0193
Study First Received: July 14, 2009
Last Updated: October 8, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
Disease-Free Survival

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Cediranib
Cisplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014