Vandetanib Gemcitabine Or Placebo Plus Gemcitabine Or Vandetanib Monotherapy In Advanced Biliary Tract Cancer

A Randomized, 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 Cholangiocarcinoma and Ampullary Carcinoma)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00753675

Acronym

VANGOGH

Enrollment

174

Registered

2008-09-16

Start date

2008-10-31

Completion date

2012-09-30

Last updated

2016-10-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ampullary Carcinoma, Biliary Tract Cancer, Cancer Of The Extrahepatic Bile Duct, Gallbladder Cancer

Keywords

Intrahepatic, Cholangiocarcinoma, Vandetanib, Zactima, Advanced, Biliary, Tract, Gallbladder, Extrahepatic Bile Duct, Intrahepatic Cholangiocarcinoma, Ampullary Carcinoma

Brief summary

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.

Interventions

DRUGZD6474, Vandetanib

300 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first

DRUGGemcitabine

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

DRUGPlacebo 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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Progression Free Survival	up to 1032 days	Progression was defined as Time from the date of first dose of study medication to progression of disease, or death (it also includes patients who are lost to follow-up or have withdrawn consent) and evaluated with RECIST criteria as an increase of at least 20% in the sum of longest diameter (LD) of target lesion(s) taking as reference the smallest sum of LD since the treatment started or any new lesion(s).

Secondary

Measure	Time frame	Description
Objective Tumor Response Rate (CR+PR),	up to 1032 days	Objective Tumor Response Rate was defined as complete response (CR) + partial response (PR) evaluated by RECIST. CR was defined as disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of longest diameters (LD) of target lesion(s) taking as reference the baseline sum of LD
Disease Control Rate (CR+PR+SD)	up to 1032 days	DCR is the sum of patients with a best overall CR, PR or SD (\>=8 weeks) by the patient in the analysis
Duration of Response (DOR)	up to 1032 days	DOR is defined from the date of first documentation of response until date of PD or death
Overall Survival	up to 1032 days	OS is defined from the date of randomization to death

Countries

Italy

Participant flow

Recruitment details

180 subjects were screened at 19 sites and 174 were randomized

Participants by arm

Arm	Count
Arm A Vandetanib 300 mg Vandetanib 300 mg as a once daily oral dose, from Day 1	59
Arm B Vandetanib 100mg + Gemcitab 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)	58
ARM C Placebo+ Gemcitabine 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).	56
Total	173

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	11	9	4
Overall Study	Death	1	2	4
Overall Study	Lost to Follow-up	1	0	0
Overall Study	Objective progression of disease	35	35	35
Overall Study	other reason	11	12	13
Overall Study	Withdrawal by Subject	0	1	0

Baseline characteristics

Characteristic	Arm A Vandetanib 300 mg	Arm B Vandetanib 100mg + Gemcitab	ARM C Placebo+ Gemcitabine	Total
Age, Continuous	62.39 years STANDARD_DEVIATION 10.108	64.41 years STANDARD_DEVIATION 9.455	63.95 years STANDARD_DEVIATION 8.764	63.57 years STANDARD_DEVIATION 9.456
Sex: Female, Male Female	34 Participants	27 Participants	31 Participants	92 Participants
Sex: Female, Male Male	25 Participants	31 Participants	25 Participants	81 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	57 / 59	53 / 58	50 / 56
serious Total, serious adverse events	16 / 59	15 / 58	12 / 56

Arm	Measure	Value (MEDIAN)
Arm A Vandetanib 300 mg	Overall Survival	228 Days
Arm B Vandetanib 100mg + Gemcitab	Overall Survival	284 Days
ARM C Placebo+ Gemcitabine	Overall Survival	307 Days

Source: ClinicalTrials.gov · Data processed: Mar 18, 2026