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

NCT00939848 | Completed Phase 2 DMC

• 1 other identifier: ABC-03 09/0193
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 2

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.

Conditions

Biliary Tract Neoplasms

Keywords

Disease-Free Survival

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  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

  3 years minimum

Study Arms (2)

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).

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)

Drug: gemcitabine; Drug: cisplatin; Drug: Placebo

Interventions

gemcitabine DRUG

gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression

Arm A

cisplatin DRUG

cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 24 weeks in the absence of disease progression

Arm A

Placebo DRUG

20mg od (continuous dosing) until evidence of disease progression has been confirmed

Arm A

cediranib DRUG

cediranib 20mg oral daily (continuous dosing)until evidence of disease progression has been confirmed

Also known as: AZD2171

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• AstraZeneca: collaborator

Study Sites (2)

University College London Hospitals NHS Foundation Trust

London, NW1 2PQ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Valle 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.

  PMID: 26179201 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

Gemcitabine; Cisplatin; cediranib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Juan Valle, MD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: July 15, 2009
• Study Start: April 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2014
• Last Updated: October 27, 2014

Record last verified: 2012-10

Locations

GB (2)