Vandetanib Gemcitabine Or Placebo Plus Gemcitabine Or Vandetanib Monotherapy In Advanced Biliary Tract Cancer - Full Text View

Sponsored by:	AstraZeneca
Information provided by:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00753675

Purpose

The primary objective of the trial is to determine the efficacy of VANDETANIB monotherapy or VANDETANIB plus GEMCITABINE or PLACEBO plus GEMCITABINE in prolonging the progression-free survival (PFS) at the trial closure in patients with advanced (unresectable or metastatic) biliary tract cancer.

Condition	Intervention	Phase
Biliary Tract Cancer Gallbladder Cancer Cancer Of The Extrahepatic Bile Duct Ampullary Carcinoma	Drug: ZD6474, VANDETANIB Drug: GEMCITABINE Drug: Placebo matching ZD6474	Phase II

MedlinePlus related topics: Cancer Gallbladder Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine Vandetanib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	A RANDOMISED, MULTICENTRE, PHASE II, PARALLEL-GROUP TRIAL OF VANDETANIB MONOTHERAPY OR VANDETANIB IN COMBINATION WITH GEMCITABINE VERSUS GEMCITABINE PLUS VANDETANIB MATCHING PLACEBO IN SUBJECTS WITH ADVANCED BILIARY TRACT CANCER (GALLBLADDER CANCER, CANCER OF THE EXTRAHEPATIC BILE DUCT, INTRAHEPATIC

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Progression Free Survival [ Time Frame: RECIST is carried out at screening and every 6 weeks during the study until objective disease progression up to week 18 and every 8 weeks thereafter. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

objective tumor response rate (CR+PR), disease control rate (CR+PR+SD) and duration of response (DOR) [ Time Frame: RECIST is carried out at screening and every 6 weeks during the study until objective disease progression up to week 18 and every 8 weeks thereafter. ] [ Designated as safety issue: No ]
overall survival [ Time Frame: Assessments for survival must be made at the 60 day follow-up visit and then every 3 months, unless the patient withdraws consent. ] [ Designated as safety issue: No ]
potential surrogate markers related to VEGFR and EGFR pathways from blood and tumor, to determine if pre-treatment levels or treatment-induced changes in these markers correlate with clinical outcome [ Time Frame: The first biopsy will be obtained prior to the first dose of study drug, and the second biopsy will be obtained at Week 13. Blood samples for biomarker analysis will be collected as for RECIST ] [ Designated as safety issue: No ]

Estimated Enrollment:	174
Study Start Date:	October 2008
Estimated Study Completion Date:	April 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental VANDETANIB 300 mg as a once daily oral dose, from Day 1	Drug: ZD6474, VANDETANIB 300 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
B: Experimental GEMCITABINE administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus VANDETANIB 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue GEMCITABINE plus VANDETANIB / PLACEBO or to continue VANDETANIB / PLACEBO monotherapy)	Drug: ZD6474, VANDETANIB 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first Drug: GEMCITABINE administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
C: Placebo Comparator GEMCITABINE administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus VANDETANIB 100 mg MATCHING PLACEBO orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue GEMCITABINE plus VANDETANIB / PLACEBO or to continue VANDETANIB / PLACEBO monotherapy).	Drug: GEMCITABINE administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle UP to 6 cycles or UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first Drug: Placebo matching ZD6474 Placebo to match ZD6474 100 mg as a once daily oral dose, from Day 1 UNTIL disease progression or unacceptable toxicity or consent withdrawal whichever occurs first

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytologically-confirmed advanced (unresectable or metastatic) biliary tract cancer (gallbladder cancer, cancer of the extrahepatic bile duct, intrahepatic cholangiocarcinoma and ampullary carcinoma)
Patients must have measurable or evaluable but non-measurable disease
Chemotherapy-naïve (prior chemotherapy in the adjuvant setting completed more than 3 months before the trial entry is accepted).
WHO performance status 0 to 2: patients must have a WHO PS ≤ 2

Exclusion Criteria:

Patients must not have received prior systemic therapy for advanced (unresectable or metastatic) disease; prior chemotherapy in the adjuvant setting within 3 months before the trial entry is accepted
Inadequate end-organ function or Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance wit
Significant cardiovascular event (e.g. myocardial infarction, superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart disease ³2) within 3 months before entry, or presence of cardiac disease that in the opinion of
History of arrhythmia or QTc with Bazett's correction unmeasurable or ≥ 480 msec on screening ECG

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00753675

Contacts

Contact: Ettore MARI, MD	+ 39 029801522	ettore.mari@astrazeneca.com
Contact: Erica Tramontana, MD	+39 022413491	e.tramontana@hyperphar.com

Locations

Italy
Research Site	Not yet recruiting
Rozzano, Italy
Research Site	Not yet recruiting
Ancona, Italy
Research Site	Not yet recruiting
Aviano, Italy
Research Site	Not yet recruiting
Bari, Italy
Research Site	Not yet recruiting
Bergamo, Italy
Research Site	Not yet recruiting
Brescia, Italy
Research Site	Not yet recruiting
Firenze, Italy
Research Site	Not yet recruiting
Livorno, Italy
Research Site	Not yet recruiting
Treviso, Italy
Research Site	Not yet recruiting
Palermo, Italy
Research Site	Not yet recruiting
Parma, Italy
Research Site	Not yet recruiting
Reggio Emilia, Italy
Research Site	Recruiting
Roma, Italy
Research Site	Not yet recruiting
Sassari, Italy
Research Site	Not yet recruiting
Torino, Italy
Research Site	Not yet recruiting
Milano, Italy

Sponsors and Collaborators

AstraZeneca

Investigators

Study Chair:	Armando Santoro, MD	Istituto Clinico Humanitas - ROZZANO (MI) ITALY
Principal Investigator:	Lorenza Rimassa, MD	Istituto Clinico Humanitas - ROZZANO (MI) ITALY
Study Director:	Peter Langmuir, MD	AstraZeneca

More Information

Publications:

Wedge SR, Ogilvie DJ, Dukes M, Kendrew J, Chester R, Jackson JA, Boffey SJ, Valentine PJ, Curwen JO, Musgrove HL, Graham GA, Hughes GD, Thomas AP, Stokes ES, Curry B, Richmond GH, Wadsworth PF, Bigley AL, Hennequin LF. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 2002 Aug 15;62(16):4645-55.

Responsible Party:	AstraZeneca Pharmaceuticals ( Peter LANGMUIR, MD ZACTIMA Medical Science Senior Director )
Study ID Numbers:	D4200L00007, EUDRACT n° 2007-003056-12
Study First Received:	September 15, 2008
Last Updated:	October 29, 2008
ClinicalTrials.gov Identifier:	NCT00753675
Health Authority:	Italy: Ethics Committee

Keywords provided by AstraZeneca:

Intrahepatic
Cholangiocarcinoma
Vandetanib
Zactima
Advanced
Biliary

Tract
Gallbladder
Extrahepatic Bile Duct
Intrahepatic Cholangiocarcinoma
Ampullary Carcinoma

Study placed in the following topic categories:

Gallbladder Diseases
Cholangiocarcinoma
Biliary Tract Neoplasms
Digestive System Neoplasms
Biliary tract cancer
Carcinoma
Gall bladder cancer

Digestive System Diseases
Biliary Tract Diseases
Gastrointestinal Neoplasms
Gallbladder Neoplasms
Gemcitabine
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009