ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer (ZODIAC)
24 août 2016 mis à jour par: Genzyme, a Sanofi Company
A Phase III, Randomized, Double-Blinded, Multi-Center, Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination With ZD6474 (ZACTIMA™) Versus Docetaxel (TAXOTERE™) With Placebo in Subjects With Locally Advanced or Metastatic NSCLC
This large phase III clinical study is studying the effect of vandetanib (ZACTIMA) in treating non-small cell lung cancer (NSCLC). Vandetanib is a new type of agent that targets the blood supply to a cancer tumour (through it's anti-vascular endothelial growth factor receptor (VEGFR) properties) and the tumour cells themselves (through it's anti-endothelial growth factor receptor (EGFR) actions). This study will look at the effects of vandetanib in lung cancer patients who have had their cancer re-appear after treatment with standard chemotherapy.
This clinical study will test if the vandetanib anti-VEGF and anti-EGFR characteristics can deliver longer improved progression free survival and improved overall survival than docetaxel (Taxotere) alone.
All patients participating this clinical study will receive treatment with docetaxel, a commonly used treatment for recurrent non-small cell lung cancer.
In addition, some patients will also receive vandetanib (ZACTIMA), an anti-EGFR / anti-VEGF agent.
Recent clinical research shows that vascular endothelial growth factor receptor (VEGFR) inhibition, when used with standard chemotherapy, can lead to increased survival in advanced non-small cell lung cancer (NSCLC) patients.
Other research shows that epidermal growth factor receptor (EGFR) inhibitors, like erlotinib (Tarceva) can also increase overall non-small cell lung cancer survival by killing tumour cells and stopping them from dividing.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
1690
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Bad Berka, Allemagne
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Berlin, Allemagne
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Essen, Allemagne
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Großhansdorf, Allemagne
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Halle, Allemagne
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Hamburg, Allemagne
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Heidelberg, Allemagne
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Köln, Allemagne
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Oldenburg, Allemagne
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Ulm, Allemagne
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Wiesbaden, Allemagne
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Bahía Blanca, Argentine
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Capital Federal, Argentine
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Ciudad de Buenos Aires, Argentine
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Mendoza, Argentine
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Rosario, Argentine
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Brussels (Jette), Belgique
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Brussels (Woluwé-St-Lambert), Belgique
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Edegem, Belgique
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Genk, Belgique
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Liege, Belgique
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Fortaleza, Brésil
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Goiânia, Brésil
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Porto Alegre, Brésil
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Rio de Janeiro, Brésil
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Sao Paulo, Brésil
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Quebec, Canada
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Alberta
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Edmonton, Alberta, Canada
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New Brunswick
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Moncton, New Brunswick, Canada
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Nova Scotia
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Halifax, Nova Scotia, Canada
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Ontario
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Kitchener, Ontario, Canada
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Quebec
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Laval, Quebec, Canada
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Beijing, Chine
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Chongqing, Chine
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Guangzhou, Chine
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Nanjing, Chine
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Shanghai, Chine
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Wuhan, Chine
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Seoul, Corée, République de
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København Ø, Danemark
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Odense, Danemark
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Roskilde, Danemark
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Vejle, Danemark
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A Coruña, Espagne
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Alicante, Espagne
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Zaragoza, Espagne
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Bordeaux Cedex, France
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Boulogne Billancourt, France
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Caen Cedex, France
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Dijon, France
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Nancy, France
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Paris, France
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Pierre Benite Cedex, France
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Saint Herblain, France
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Athens, Grèce
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Heraklion, Grèce
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Ahmedabad, Inde
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Chennai, Inde
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Hyderabad, Inde
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Kolkata, Inde
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New Delhi, Inde
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Pune, Inde
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Vellore, Inde
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Jakarta Timur, Indonésie
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Yogyakarta, Indonésie
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Ancona, Italie
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Avellino, Italie
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Bologna, Italie
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Genova, Italie
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Mantova, Italie
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Napoli, Italie
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Orbassano, Italie
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Parma, Italie
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Perugia, Italie
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Pisa, Italie
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Reggio Emilia, Italie
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Akashi-shi, Japon
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Fukuoka, Japon
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Fukuoka-shi, Japon
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Isehara-shi, Japon
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Kobe-shi, Japon
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Koto-ku, Japon
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Kumamoto-shi, Japon
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Matsuyama-shi, Japon
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Nagoya-shi, Japon
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Okayama-shi, Japon
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Okazaki-shi, Japon
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Osaka-shi, Japon
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Osakasayama-shi, Japon
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Sakai-shi, Japon
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Sapporo-shi, Japon
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Shinjuku-ku, Japon
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Sunto-gun, Japon
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Toyonaka, Japon
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Ube-shi, Japon
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Utsunomiya-shi, Japon
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Yokohama-shi, Japon
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Graz, L'Autriche
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Grimmenstein, L'Autriche
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Innsbruck, L'Autriche
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Linz, L'Autriche
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Wels, L'Autriche
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Wien, L'Autriche
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Coimbra, Le Portugal
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Funchal, Le Portugal
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Lisboa, Le Portugal
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Porto, Le Portugal
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Vila Nova de Gaia, Le Portugal
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Kubang Kerian, Malaisie
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Nilai, Malaisie
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Penang, Malaisie
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Durango, Mexique
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Morelia, Mexique
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Toluca, Mexique
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Amsterdam, Pays-Bas
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Den Bosch, Pays-Bas
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Groningen, Pays-Bas
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Maastricht, Pays-Bas
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Singapore, Singapour
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Chiang Mai, Thaïlande
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Ankara, Turquie
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Istanbul, Turquie
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Izmir, Turquie
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Hanoi city, Viêt Nam
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Ho Chi Minh city, Viêt Nam
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California
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Fullerton, California, États-Unis
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Los Angeles, California, États-Unis
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Northridge, California, États-Unis
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Colorado
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Colorado Springs, Colorado, États-Unis
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Connecticut
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Norwalk, Connecticut, États-Unis
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Florida
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Ocala, Florida, États-Unis
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Georgia
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Marietta, Georgia, États-Unis
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Illinois
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Joliet, Illinois, États-Unis
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Park Ridge, Illinois, États-Unis
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Kansas
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Hutchinson, Kansas, États-Unis
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Kentucky
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Louisville, Kentucky, États-Unis
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Massachusetts
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Boston, Massachusetts, États-Unis
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Michigan
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Ann Arbor, Michigan, États-Unis
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Missouri
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St. Louis, Missouri, États-Unis
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Nevada
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Henderson, Nevada, États-Unis
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New York
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Albany, New York, États-Unis
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Armonk, New York, États-Unis
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New York, New York, États-Unis
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North Carolina
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Durham, North Carolina, États-Unis
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Hickory, North Carolina, États-Unis
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Oregon
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Portland, Oregon, États-Unis
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Texas
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Austin, Texas, États-Unis
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Houston, Texas, États-Unis
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Utah
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Ogden, Utah, États-Unis
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Virginia
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Alexandria, Virginia, États-Unis
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Salem, Virginia, États-Unis
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Washington
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Vancouver, Washington, États-Unis
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
Lung cancer patients who answer true to the following statements are eligible to join this clinical study.
- I have a confirmed diagnosis of locally advanced or metastatic non small cell lung cancer (Stage IIIb - IV)
- I have had 1st line anti-cancer therapy. Previous treatment with Avastin (bevacizumab) in first line NSCLC is allowed.
Exclusion Criteria:
Lung cancer patients who answer true to the following are NOT eligible to join this clinical study.
- I do not have non small cell lung cancer (NSCLC)
- I have received treatment with docetaxel (Taxotere). Prior treatment with paclitaxel is acceptable.
- I have received 2nd line anti-cancer therapy (For example, patients with previous 2nd line non small cell lung cancer (NSCLC) treatment with Tarceva (erlotinib, OSI-744), Alimta (pemetrexed) are not eligible)
- I have been treated with VEGFR-tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, other VEGF TKIs). Previous treatment with Avastin (bevacizumab) in 1st line non small cell lung cancer is permitted.
- I have a history of uncontrolled irregular heartbeat
- I have a history of high blood pressure which has not been controlled with medication If you are unsure of the meaning of the inclusion and exclusion criteria above, please contact the call center number for help.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 2
Vandétanib + Docétaxel
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infusion
Autres noms:
oral
Autres noms:
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Comparateur actif: 1
Docetaxel monotherapy
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infusion
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Progression-Free Survival (PFS) in the Overall Population
Délai: RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
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Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.
Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
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RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
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Progression-Free Survival (PFS) in the Female Population
Délai: RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
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Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment.
Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
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RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Overall Survival (OS) in the Overall Population
Délai: Time to death in months
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Overall survival is defined as the time from date of randomization until death.
Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
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Time to death in months
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Overall Survival (OS) in the Female Population
Délai: Time to death in months
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Overall survival is defined as the time from date of randomization until death.
Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
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Time to death in months
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Objective Response Rate (ORR)
Délai: Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0.
CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.
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Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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Disease Control Rate (DCR)
Délai: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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Disease control rate is defined as the number of patients who achieved disease control at least 6 weeks following randomisation.
Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 weeks as determined according to RECIST 1.0.
CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 6 is assigned to patients who have not responded and have no evidence of progression at least 6 weeks after randomisation.
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RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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Duration of Response (DoR)
Délai: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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Response is defined as a confirmed best objective response of CR or PR.
Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)
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RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
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Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
Délai: FACT-L questionnaires are to be administered every 3 weeks after randomisation
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The lung cancer subscale (LCS) consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days. |
FACT-L questionnaires are to be administered every 3 weeks after randomisation
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Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
Délai: FACT-L questionnaires are to be administered every 3 weeks after randomisation
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The pulmonary symptom index (PSI) consists of 4 items of the LCS relating to pulmonary symptoms (i.e. 3 items relating to breathing/dyspnea, and 1 item relating to cough). The PSI score is the sum of the scores from the 4 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days. |
FACT-L questionnaires are to be administered every 3 weeks after randomisation
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: Contact-US@sanofi.com, Sanofi
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- Platt A, Morten J, Ji Q, Elvin P, Womack C, Su X, Donald E, Gray N, Read J, Bigley G, Blockley L, Cresswell C, Dale A, Davies A, Zhang T, Fan S, Fu H, Gladwin A, Harrod G, Stevens J, Williams V, Ye Q, Zheng L, de Boer R, Herbst RS, Lee JS, Vasselli J. A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies. BMC Cancer. 2015 Mar 23;15:171. doi: 10.1186/s12885-015-1146-8.
- Lombard A, Mistry H, Aarons L, Ogungbenro K. Dose individualisation in oncology using chemotherapy-induced neutropenia: Example of docetaxel in non-small cell lung cancer patients. Br J Clin Pharmacol. 2021 Apr;87(4):2053-2063. doi: 10.1111/bcp.14614. Epub 2020 Dec 19.
- Heymach JV, Lockwood SJ, Herbst RS, Johnson BE, Ryan AJ. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer. Ann Oncol. 2014 Oct;25(10):1941-1948. doi: 10.1093/annonc/mdu269. Epub 2014 Jul 23.
- Herbst RS, Sun Y, Eberhardt WE, Germonpre P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. doi: 10.1016/S1470-2045(10)70132-7.
Liens utiles
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mai 2006
Achèvement primaire (Réel)
1 août 2008
Achèvement de l'étude (Réel)
1 mars 2014
Dates d'inscription aux études
Première soumission
6 avril 2006
Première soumission répondant aux critères de contrôle qualité
6 avril 2006
Première publication (Estimation)
10 avril 2006
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
30 septembre 2016
Dernière mise à jour soumise répondant aux critères de contrôle qualité
24 août 2016
Dernière vérification
1 août 2016
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies des voies respiratoires
- Tumeurs
- Maladies pulmonaires
- Tumeurs par site
- Tumeurs des voies respiratoires
- Tumeurs thoraciques
- Carcinome bronchique
- Tumeurs bronchiques
- Tumeurs pulmonaires
- Carcinome pulmonaire non à petites cellules
- Mécanismes moléculaires de l'action pharmacologique
- Agents antinéoplasiques
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Docétaxel
Autres numéros d'identification d'étude
- D4200C00032
- 6474IL/0032
- 2005-004749-32 (Numéro EudraCT)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .