ZETA
An International, Phase III, Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 (ZACTIMATM) Versus Placebo in Subjects With Unresectable Locally Advanced or Metastatic Medullary Thyroid Cancer
Phase 3N = 331NCT00410761
- Population
- Advanced medullary thyroid cancer (locally advanced or metastatic); mean age 52 years, 90% sporadic, 95% metastatic (abstract)
- Design
- Randomised (2:1), double-blind, placebo-controlled phase 3 trial of vandetanib 300 mg/day versus placebo; on objective disease progression patients could elect open-label vandetanib. Primary endpoint progression-free survival by independent central RECIST assessment. Randomisation December 2006 to November 2007; data cutoff July 2009.
- Primary endpoint
- PFS
- Arms
- Vandetanib (experimental, n = 231): Vandetanib 300 mg orally once daily
- Placebo (control, n = 100): Placebo
- People
- Wells SA Jr, senior author Schlumberger MJ
PFSHR 0.46 (95% CI 0.31–0.69)OSHR 0.89 (95% CI 0.48–1.65)PFSHR 0.43 (95% CI 0.28–0.64)OSHR 1.08 (95% CI 0.72–1.61)Δ ORR+35 points
Show the numbers
| Endpoint | Analysis | Vandetanib | Placebo | Effect |
|---|---|---|---|---|
| PFSAll randomised patients (231 vandetanib, 100 placebo); the abstract does not name the analysis population | primarymedian follow-up 24 monthsWells 2012 | — | — | HR 0.46 (95% CI 0.31–0.69)P<.001At the July 2009 cutoff 37% of patients had progressed and 15% had died. Objective response rate, disease control rate and biochemical response also favoured vandetanib (P<.001, P=.001 and P<.001); the abstract gives no response percentages. Any-grade adverse events, vandetanib versus placebo: diarrhoea 56% v 26%, rash 45% v 11%, nausea 33% v 16%, hypertension 32% v 5%, headache 26% v 9%. The abstract reports no median PFS for either arm. |
| OSAll randomised patients (231 vandetanib, 100 placebo) | interimWells 2012 | — | — | HR 0.89 (95% CI 0.48–1.65)Overall survival data were immature at the data cutoff; the abstract states that a final survival analysis would take place when half of patients had died. |
| PFSPost hoc subgroup: symptomatic and progressive disease at baseline | exploratoryKreissl 2020 | — | — | HR 0.43 (95% CI 0.28–0.64)P<.0001Post hoc analysis of 184 of the 331 patients; PFS here was determined from the local investigator's measurements, not from independent central review. |
| OSPost hoc subgroup: symptomatic and progressive disease at baseline | exploratoryKreissl 2020 | — | — | HR 1.08 (95% CI 0.72–1.61)P=.71Post hoc analysis of 184 patients. |
| ORRPost hoc subgroup: symptomatic and progressive disease at baseline | exploratoryKreissl 2020 | 37% | 2% | Post hoc analysis of 184 patients; objective response rate in the vandetanib and placebo arms. |
| Endpoint | Analysis | Vandetanib | Placebo | Effect |
|---|---|---|---|---|
| PFSAll randomised patients (231 vandetanib, 100 placebo); the abstract does not name the analysis population | primarymedian follow-up 24 monthsWells 2012 | — | — | HR 0.46 (95% CI 0.31–0.69)P<.001At the July 2009 cutoff 37% of patients had progressed and 15% had died. Objective response rate, disease control rate and biochemical response also favoured vandetanib (P<.001, P=.001 and P<.001); the abstract gives no response percentages. Any-grade adverse events, vandetanib versus placebo: diarrhoea 56% v 26%, rash 45% v 11%, nausea 33% v 16%, hypertension 32% v 5%, headache 26% v 9%. The abstract reports no median PFS for either arm. |
| OSAll randomised patients (231 vandetanib, 100 placebo) | interimWells 2012 | — | — | HR 0.89 (95% CI 0.48–1.65)Overall survival data were immature at the data cutoff; the abstract states that a final survival analysis would take place when half of patients had died. |
| PFSPost hoc subgroup: symptomatic and progressive disease at baseline | exploratoryKreissl 2020 | — | — | HR 0.43 (95% CI 0.28–0.64)P<.0001Post hoc analysis of 184 of the 331 patients; PFS here was determined from the local investigator's measurements, not from independent central review. |
| OSPost hoc subgroup: symptomatic and progressive disease at baseline | exploratoryKreissl 2020 | — | — | HR 1.08 (95% CI 0.72–1.61)P=.71Post hoc analysis of 184 patients. |
| ORRPost hoc subgroup: symptomatic and progressive disease at baseline | exploratoryKreissl 2020 | 37% | 2% | Post hoc analysis of 184 patients; objective response rate in the vandetanib and placebo arms. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.46 | 0.31–0.69 |
| OS | 0.89 | 0.48–1.65 |
| PFS | 0.43 | 0.28–0.64 |
| OS | 1.08 | 0.72–1.61 |
Appears in
Sources
Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134-41.
Kreissl MC, Bastholt L, Elisei R, Haddad R, Hauch O, Jarząb B, et al. Efficacy and Safety of Vandetanib in Progressive and Symptomatic Medullary Thyroid Cancer: Post Hoc Analysis From the ZETA Trial. J Clin Oncol. 2020;38(24):2773-2781.