Biliary Tract NeoplasmsPhase 2/3ABC-03NCT00939848
Cediranib Versus Placebo Plus Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers
A Phase 2/3 study testing gemcitabine, cisplatin and cediranib in people with Biliary Tract Neoplasms, run by University College, London at 2 sites in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Biliary Tract Neoplasms
- What is being tested?
- gemcitabine, cisplatin and cediranib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Apr 2011to Sep 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
University College London Hospitals NHS Foundation Trust
London, NW1 2PQ
The Christie NHS Foundation Trust
Manchester, M20 4BX
About this study
Official title: Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers
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.
Read the 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.
- Conditions
- Biliary Tract Neoplasms
- Being tested
- gemcitabine, cisplatin, Placebo, cediranib
- Keywords
- Disease-Free Survival
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gemcitabineDrug
gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
cisplatinDrug
cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
PlaceboDrug
20mg od (continuous dosing) until evidence of disease progression has been confirmed
cisplatinDrug
cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
cediranibDrug
Also called AZD2171
cediranib 20mg oral daily (continuous dosing)until evidence of disease progression has been confirmed
gemcitabineDrug
gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression
| Study group | Role | What they receive |
|---|---|---|
| B | Experimental | 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). Receives: Drug: cisplatin; Drug: cediranib; Drug: gemcitabine |
| Arm A | Placebo comparator | 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) Receives: Drug: gemcitabine; Drug: cisplatin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Measured: six months
Secondary outcomes (1)
• 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
Measured: 3 years minimum
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2009 (estimated)
- Study startApr 2011
- Primary completionSep 2012
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract NeoplasmsStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Juan Valle, MD, Principal investigator, The Christie NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00939848
- Sponsor's protocol ID
- ABC-03 09/0193
- Acronym
- ABC-03
- Status last verified
- Oct 2012
- First submitted
- 14 Jul 2009
- Last updated
- 27 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lamarca A, Ross P, Wasan HS, Hubner RA, McNamara MG, Lopes A, Palmer DH, Valle JW, Bridgewater J. Advanced extrahepatic cholangiocarcinoma and gallbladder cancer: Post-hoc analysis of the ABC-01, -02 and -03 clinical trials. JHEP Rep. 2026 Jul;8(7):101833. doi: 10.1016/j.jhepr.2026.101833. Epub 2026 Mar 24.
PubMed 41887529Valle JW, Wasan H, Lopes A, Backen AC, Palmer DH, Morris K, Duggan M, Cunningham D, Anthoney DA, Corrie P, Madhusudan S, Maraveyas A, Ross PJ, Waters JS, Steward WP, Rees C, Beare S, Dive C, Bridgewater JA. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncol. 2015 Aug;16(8):967-78. doi: 10.1016/S1470-2045(15)00139-4. Epub 2015 Jul 12.
PubMed 26179201
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Phase II Trial of Cediranib (AZD2171) Versus Placebo in Addition to Cisplatin/Gemcitabine Chemotherapy for Patients With Advanced Biliary Tract Cancers
- ClinicalTrials.gov ID
- NCT00939848
- Acronym / sponsor ID
- ABC-03 / ABC-03 09/0193
- Conditions
- Biliary Tract Neoplasms
- Keywords
- Disease-Free Survival
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Apr 2011
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 15 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| B | Experimental | Drug: cisplatin, Drug: cediranib, Drug: gemcitabineThe 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). |
| Arm A | Placebo comparator | Drug: gemcitabine, Drug: cisplatin, Drug: PlaceboThe 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gemcitabinegemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression | Drug | Arm A |
| cisplatincisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression | Drug | Arm A |
| Placebo20mg od (continuous dosing) until evidence of disease progression has been confirmed | Drug | Arm A |
| cisplatincisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression | Drug | B |
| cediranibAlso: AZD2171cediranib 20mg oral daily (continuous dosing)until evidence of disease progression has been confirmed | Drug | B |
| gemcitabinegemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression | Drug | B |
Primary outcome
Progression free survival
Time frame: six months
1 secondary outcome
• 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2014.
- Derived from this study: PubMed 41887529Lamarca A, Ross P, Wasan HS, Hubner RA, McNamara MG, Lopes A, Palmer DH, Valle JW, Bridgewater J. Advanced extrahepatic cholangiocarcinoma and gallbladder cancer: Post-hoc analysis of the ABC-01, -02 and -03 clinical trials. JHEP Rep. 2026 Jul;8(7):101833. doi: 10.1016/j.jhepr.2026.101833. Epub 2026 Mar 24.
- Derived from this study: PubMed 26179201Valle JW, Wasan H, Lopes A, Backen AC, Palmer DH, Morris K, Duggan M, Cunningham D, Anthoney DA, Corrie P, Madhusudan S, Maraveyas A, Ross PJ, Waters JS, Steward WP, Rees C, Beare S, Dive C, Bridgewater JA. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncol. 2015 Aug;16(8):967-78. doi: 10.1016/S1470-2045(15)00139-4. Epub 2015 Jul 12.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Valle, MD principal investigator
The Christie NHS Foundation Trust
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing gemcitabine, cisplatin and cediranib in people with Biliary Tract Neoplasms, run by University College, London at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00939848, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2014.