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

Armando Santoro, V. Gebbia, T. Pressiani, A. Testa, N. Personeni, E. Arrivas Bajardi, P. Foa, A. Buonadonna, K. Bencardino, C. Barone, D. Ferrari, A. Zaniboni, M. C. Tronconi, G. Cartenì, M. Milella, A. Comandone, S. Ferrari, L. Rimassa

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Abstract

Background: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. Patients and methods: Patients were randomized in a 1:1:1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m2 was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. Results: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). Conclusions: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs.

Original languageEnglish
Pages (from-to)542-547
Number of pages6
JournalAnnals of Oncology
Volume26
Issue number3
DOIs
Publication statusPublished - 2015

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gemcitabine
Biliary Tract Neoplasms
Placebos
Disease-Free Survival
Therapeutics
Safety
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Italy
Multicenter Studies
Survival Rate

Keywords

  • Advanced biliary tract cancer
  • Gemcitabine
  • Vandetanib

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

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. / Santoro, Armando; Gebbia, V.; Pressiani, T.; Testa, A.; Personeni, N.; Arrivas Bajardi, E.; Foa, P.; Buonadonna, A.; Bencardino, K.; Barone, C.; Ferrari, D.; Zaniboni, A.; Tronconi, M. C.; Cartenì, G.; Milella, M.; Comandone, A.; Ferrari, S.; Rimassa, L.

In: Annals of Oncology, Vol. 26, No. 3, 2015, p. 542-547.

Research output: Contribution to journalArticle

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title = "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",
abstract = "Background: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. Patients and methods: Patients were randomized in a 1:1:1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m2 was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. Results: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95{\%} confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6{\%} in V arm, 91.4{\%} in the V/G arm and 89.3{\%} in the G/P arm). Conclusions: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs.",
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T1 - 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

T2 - The VanGogh study

AU - Santoro, Armando

AU - Gebbia, V.

AU - Pressiani, T.

AU - Testa, A.

AU - Personeni, N.

AU - Arrivas Bajardi, E.

AU - Foa, P.

AU - Buonadonna, A.

AU - Bencardino, K.

AU - Barone, C.

AU - Ferrari, D.

AU - Zaniboni, A.

AU - Tronconi, M. C.

AU - Cartenì, G.

AU - Milella, M.

AU - Comandone, A.

AU - Ferrari, S.

AU - Rimassa, L.

PY - 2015

Y1 - 2015

N2 - Background: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared with vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. Patients and methods: Patients were randomized in a 1:1:1 ratio to three treatment groups: vandetanib 300 mg monotherapy (V), vandetanib 100 mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300 mg or 100 mg) or placebo was given in single oral daily doses. Gemcitabine 1000 mg/m2 was i.v. infused on day 1 and day 8 of each 21-day cycle. The primary end point was progression-free survival (PFS). Secondary end points were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. Results: A total of 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225), respectively, for the V, V/G and G/P treatment groups, with no statistical difference among them (P = 0.18). No statistical difference between treatments was observed for secondary end points, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the three groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). Conclusions: Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs.

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KW - Advanced biliary tract cancer

KW - Gemcitabine

KW - Vandetanib

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