Biliary Tract CancerPhase 2VANGOGHNCT00753675

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

A Phase 2 study testing ZD6474, Vandetanib and Gemcitabine in people with Biliary Tract Cancer and Gallbladder Cancer, run by Genzyme, a Sanofi Company at 15 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Biliary Tract Cancer, Gallbladder Cancer, Cancer Of The Extrahepatic Bile Duct
What is being tested?: ZD6474, Vandetanib and Gemcitabine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 174 participants
Where: 15 sitesItaly
Study dates: Oct 2008to Sep 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

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

Who cannot join

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

Trial locations and contacts

15 sites in 1 country.

City, postcode or hospital

15 sites in 1 country

Italy15 sites

Research Site
Ancona
Research Site
Aviano, PN
Research Site
Brescia, BS
Research Site
Florence, FI
Research Site
Genova, GE
Research Site
Livorno
Research Site
Milan, Mi
Research Site
Naples
Research Site
Palermo, PA
Research Site
Parma, PR
Research Site
Pisa
Research Site
Ravenna
Research Site
Reggio Emilia, RE
Research Site
Rho
Research Site
Torino

Other trials in Italy

About this study

Official title: 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)

Conditions: Biliary Tract Cancer, Gallbladder Cancer, Cancer Of The Extrahepatic Bile Duct, Ampullary Carcinoma
Being tested: ZD6474, Vandetanib, Gemcitabine, Placebo matching ZD6474
Keywords: Intrahepatic, Cholangiocarcinoma, Vandetanib, Zactima, Advanced, Biliary, Tract, Gallbladder, Extrahepatic Bile Duct, Intrahepatic Cholangiocarcinoma, Ampullary Carcinoma
Medical subject headings: Biliary Tract Neoplasms, Gallbladder Neoplasms, Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ZD6474, VandetanibDrug
Also called Zactima
300 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
ZD6474, VandetanibDrug
Also called Zactima
100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first
GemcitabineDrug
Also called Gemzar
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
Placebo matching ZD6474Drug
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 groups in NCT00753675
Study group	Role	What they receive
A	Experimental	Vandetanib 300 mg as a once daily oral dose, from Day 1 Receives: Drug: ZD6474, Vandetanib
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) Receives: Drug: ZD6474, Vandetanib; Drug: Gemcitabine
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). Receives: Drug: Gemcitabine; Drug: Placebo matching ZD6474

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression Free Survival
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).
Measured: up to 1032 days

Secondary outcomes (4)

Objective Tumor Response Rate (CR+PR),
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
Measured: up to 1032 days
Disease Control Rate (CR+PR+SD)
DCR is the sum of patients with a best overall CR, PR or SD (>=8 weeks) by the patient in the analysis
Measured: up to 1032 days
Duration of Response (DOR)
DOR is defined from the date of first documentation of response until date of PD or death
Measured: up to 1032 days
Overall Survival
OS is defined from the date of randomization to death
Measured: up to 1032 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2008Sep 2012

First posted16 Sep 2008 (estimated)
Study startOct 2008
Primary completionSep 2012
Study completionSep 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Biliary Tract CancerStudies of the same condition, open and under way.
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
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 174 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00753675
Sponsor's protocol ID: D4200L00007
Other IDs: EUDRACT n° 2007-003056-12
Acronym: VANGOGH
Status last verified: Aug 2016
First submitted: 15 Sep 2008
Last updated: 10 Oct 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 12183421
Santoro A, Gebbia V, Pressiani T, Testa A, Personeni N, Arrivas Bajardi E, Foa P, Buonadonna A, Bencardino K, Barone C, Ferrari D, Zaniboni A, Tronconi MC, Carteni G, Milella M, Comandone A, Ferrari S, Rimassa L. A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study. Ann Oncol. 2015 Mar;26(3):542-7. doi: 10.1093/annonc/mdu576. Epub 2014 Dec 23.
PubMed 25538178

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma
Thymoma, Stomach Neoplasms
Active, not recruitingPhase 2
Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)
Pancreatic Cancer, Hepatocellular Cancer
Not yet recruitingPhase 3
Hepatic Arterial Infusion Chemotherapy Versus Capecitabine as Adjuvant Therapy for Resected Biliary Tract Cancer
Biliary Tract Cancer, Cholangiocarcinoma

All Biliary Tract Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT00753675
Acronym / sponsor ID: VANGOGH / D4200L00007
Conditions: Biliary Tract Cancer, Gallbladder Cancer, Cancer Of The Extrahepatic Bile Duct, Ampullary Carcinoma
Keywords: Intrahepatic, Cholangiocarcinoma, Vandetanib, Zactima, Advanced, Biliary, Tract, Gallbladder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 174 participants (actual)
Lead sponsor: Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: Oct 2008
Primary completion: Sep 2012 (actual)
Study completion: Sep 2012 (actual)
First posted: 16 Sep 2008 (estimated)
Results: Posted 28 Nov 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
A	Experimental	Drug: ZD6474, VandetanibVandetanib 300 mg as a once daily oral dose, from Day 1
B	Experimental	Drug: ZD6474, Vandetanib, Drug: GemcitabineGemcitabine 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)
C	Placebo comparator	Drug: Gemcitabine, Drug: Placebo matching ZD6474Gemcitabine 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (4 listed)

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

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
ZD6474, VandetanibAlso: Zactima300 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first	Drug	A
ZD6474, VandetanibAlso: Zactima100 mg as a once daily oral dose, from Day 1 until disease progression or unacceptable toxicity or consent withdrawal whichever occurs first	Drug	B
GemcitabineAlso: Gemzaradministered 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	B, C
Placebo matching ZD6474Placebo 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	Drug	C

Primary outcome

Progression Free Survival
Time frame: 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).

4 secondary outcomes

Objective Tumor Response Rate (CR+PR),
Time frame: up to 1032 days
Disease Control Rate (CR+PR+SD)
Time frame: up to 1032 days
Duration of Response (DOR)
Time frame: up to 1032 days
Overall Survival
Time frame: up to 1032 days

Results and safety

Results posted to the registry on 28 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm A Vandetanib 300 mg	59	0
Arm B Vandetanib 100mg + Gemcitab	59	0
ARM C Placebo+ Gemcitabine	56	0

Primary outcome: Progression Free Survival

Time frame: up to 1032 days. Median (95% Confidence Interval). Unit: days

Measure	Arm A Vandetanib 300 mg n = 56	Arm B Vandetanib 100mg + Gemcitab n = 57	ARM C Placebo+ Gemcitabine n = 52
Value	105 (72 to 155)	114 (91 to 193)	148 (72 to 225)

Population analysed: ITT

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm A Vandetanib 300 mg	16 of 59 (27.1%)	57 of 59 (96.6%)	Not reported
Arm B Vandetanib 100mg + Gemcitab	15 of 58 (25.9%)	53 of 58 (91.4%)	Not reported
ARM C Placebo+ Gemcitabine	12 of 56 (21.4%)	50 of 56 (89.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12183421Wedge 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.
Derived from this study: PubMed 25538178Santoro A, Gebbia V, Pressiani T, Testa A, Personeni N, Arrivas Bajardi E, Foa P, Buonadonna A, Bencardino K, Barone C, Ferrari D, Zaniboni A, Tronconi MC, Carteni G, Milella M, Comandone A, Ferrari S, Rimassa L. A randomized, multicenter, phase II study of vandetanib monotherapy versus vandetanib in combination with gemcitabine versus gemcitabine plus placebo in subjects with advanced biliary tract cancer: the VanGogh study. Ann Oncol. 2015 Mar;26(3):542-7. doi: 10.1093/annonc/mdu576. Epub 2014 Dec 23.

Related trials for Biliary Tract Cancer

Active, not recruitingPhase 2/3
A Study of CTX-009 in Combination With Paclitaxel in Adult Patients With Unresectable Advanced, Metastatic or Recurrent Biliary Tract Cancers (COMPANION-002)
Biliary Tract Cancer, Cholangiocarcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Tissue Procurement and Natural History Study of Patients With Malignant Mesothelioma
Thymoma, Stomach Neoplasms
Active, not recruitingPhase 2
Durvalumab and Tremelimumab in Combination With Propranolol and Chemotherapy for Treatment of Advanced Hepatopancreabiliary Tumors (BLOCKED)
Pancreatic Cancer, Hepatocellular Cancer
Not yet recruitingPhase 3
Hepatic Arterial Infusion Chemotherapy Versus Capecitabine as Adjuvant Therapy for Resected Biliary Tract Cancer
Biliary Tract Cancer, Cholangiocarcinoma

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.

Clinical Sciences & Operations study director

Sanofi

15 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ZD6474, Vandetanib and Gemcitabine in people with Biliary Tract Cancer and Gallbladder Cancer, run by Genzyme, a Sanofi Company at 15 sites in Italy.

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 4 inclusion and 4 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 10 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Italy. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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: up to 1032 days). 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 NCT00753675, 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 10 Oct 2016.