ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer (ZODIAC)
24. august 2016 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
1690
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
-
Bahía Blanca, Argentina
- Research Site
-
Capital Federal, Argentina
- Research Site
-
Ciudad de Buenos Aires, Argentina
- Research Site
-
Mendoza, Argentina
- Research Site
-
Rosario, Argentina
- Research Site
-
-
-
-
-
Brussels (Jette), Belgia
- Research Site
-
Brussels (Woluwé-St-Lambert), Belgia
- Research Site
-
Edegem, Belgia
- Research Site
-
Genk, Belgia
- Research Site
-
Liege, Belgia
- Research Site
-
-
-
-
-
Fortaleza, Brasil
- Research Site
-
Goiânia, Brasil
- Research Site
-
Porto Alegre, Brasil
- Research Site
-
Rio de Janeiro, Brasil
- Research Site
-
Sao Paulo, Brasil
- Research Site
-
-
-
-
-
Quebec, Canada
- Research Site
-
-
Alberta
-
Edmonton, Alberta, Canada
- Research Site
-
-
New Brunswick
-
Moncton, New Brunswick, Canada
- Research Site
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada
- Research Site
-
-
Ontario
-
Kitchener, Ontario, Canada
- Research Site
-
London, Ontario, Canada
- Research Site
-
Toronto, Ontario, Canada
- Research Site
-
-
Quebec
-
Laval, Quebec, Canada
- Research Site
-
-
-
-
-
Herlev, Danmark
- Research Site
-
København Ø, Danmark
- Research Site
-
Odense, Danmark
- Research Site
-
Roskilde, Danmark
- Research Site
-
Vejle, Danmark
- Research Site
-
-
-
-
California
-
Fullerton, California, Forente stater
- Research Site
-
Los Angeles, California, Forente stater
- Research Site
-
Northridge, California, Forente stater
- Research Site
-
-
Colorado
-
Colorado Springs, Colorado, Forente stater
- Research Site
-
-
Connecticut
-
Norwalk, Connecticut, Forente stater
- Research Site
-
-
Florida
-
Ocala, Florida, Forente stater
- Research Site
-
-
Georgia
-
Marietta, Georgia, Forente stater
- Research Site
-
-
Illinois
-
Joliet, Illinois, Forente stater
- Research Site
-
Park Ridge, Illinois, Forente stater
- Research Site
-
-
Kansas
-
Hutchinson, Kansas, Forente stater
- Research Site
-
-
Kentucky
-
Louisville, Kentucky, Forente stater
- Research Site
-
-
Massachusetts
-
Boston, Massachusetts, Forente stater
- Research Site
-
-
Michigan
-
Ann Arbor, Michigan, Forente stater
- Research Site
-
-
Missouri
-
St. Louis, Missouri, Forente stater
- Research Site
-
-
Nevada
-
Henderson, Nevada, Forente stater
- Research Site
-
-
New York
-
Albany, New York, Forente stater
- Research Site
-
Armonk, New York, Forente stater
- Research Site
-
New York, New York, Forente stater
- Research Site
-
-
North Carolina
-
Durham, North Carolina, Forente stater
- Research Site
-
Hickory, North Carolina, Forente stater
- Research Site
-
-
Oregon
-
Portland, Oregon, Forente stater
- Research Site
-
-
Texas
-
Austin, Texas, Forente stater
- Research Site
-
Houston, Texas, Forente stater
- Research Site
-
-
Utah
-
Ogden, Utah, Forente stater
- Research Site
-
-
Virginia
-
Alexandria, Virginia, Forente stater
- Research Site
-
Salem, Virginia, Forente stater
- Research Site
-
-
Washington
-
Vancouver, Washington, Forente stater
- Research Site
-
-
-
-
-
Bordeaux Cedex, Frankrike
- Research Site
-
Boulogne Billancourt, Frankrike
- Research Site
-
Caen Cedex, Frankrike
- Research Site
-
Dijon, Frankrike
- Research Site
-
Nancy, Frankrike
- Research Site
-
Paris, Frankrike
- Research Site
-
Pierre Benite Cedex, Frankrike
- Research Site
-
Saint Herblain, Frankrike
- Research Site
-
-
-
-
-
Athens, Hellas
- Research Site
-
Heraklion, Hellas
- Research Site
-
-
-
-
-
Ahmedabad, India
- Research Site
-
Chennai, India
- Research Site
-
Hyderabad, India
- Research Site
-
Kolkata, India
- Research Site
-
New Delhi, India
- Research Site
-
Pune, India
- Research Site
-
Vellore, India
- Research Site
-
-
-
-
-
Jakarta Timur, Indonesia
- Research Site
-
Yogyakarta, Indonesia
- Research Site
-
-
-
-
-
Ancona, Italia
- Research Site
-
Avellino, Italia
- Research Site
-
Bologna, Italia
- Research Site
-
Genova, Italia
- Research Site
-
Mantova, Italia
- Research Site
-
Napoli, Italia
- Research Site
-
Orbassano, Italia
- Research Site
-
Parma, Italia
- Research Site
-
Perugia, Italia
- Research Site
-
Pisa, Italia
- Research Site
-
Reggio Emilia, Italia
- Research Site
-
-
-
-
-
Akashi-shi, Japan
- Research Site
-
Fukuoka, Japan
- Research Site
-
Fukuoka-shi, Japan
- Research Site
-
Isehara-shi, Japan
- Research Site
-
Kobe-shi, Japan
- Research Site
-
Koto-ku, Japan
- Research Site
-
Kumamoto-shi, Japan
- Research Site
-
Matsuyama-shi, Japan
- Research Site
-
Nagoya-shi, Japan
- Research Site
-
Okayama-shi, Japan
- Research Site
-
Okazaki-shi, Japan
- Research Site
-
Osaka-shi, Japan
- Research Site
-
Osakasayama-shi, Japan
- Research Site
-
Sakai-shi, Japan
- Research Site
-
Sapporo-shi, Japan
- Research Site
-
Shinjuku-ku, Japan
- Research Site
-
Sunto-gun, Japan
- Research Site
-
Toyonaka, Japan
- Research Site
-
Ube-shi, Japan
- Research Site
-
Utsunomiya-shi, Japan
- Research Site
-
Yokohama-shi, Japan
- Research Site
-
-
-
-
-
Beijing, Kina
- Research Site
-
Chongqing, Kina
- Research Site
-
Guangzhou, Kina
- Research Site
-
Nanjing, Kina
- Research Site
-
Shanghai, Kina
- Research Site
-
Wuhan, Kina
- Research Site
-
-
-
-
-
Seoul, Korea, Republikken
- Research Site
-
-
-
-
-
Kubang Kerian, Malaysia
- Research Site
-
Nilai, Malaysia
- Research Site
-
Penang, Malaysia
- Research Site
-
-
-
-
-
Durango, Mexico
- Research Site
-
Morelia, Mexico
- Research Site
-
Toluca, Mexico
- Research Site
-
-
-
-
-
Amsterdam, Nederland
- Research Site
-
Den Bosch, Nederland
- Research Site
-
Groningen, Nederland
- Research Site
-
Maastricht, Nederland
- Research Site
-
-
-
-
-
Coimbra, Portugal
- Research Site
-
Funchal, Portugal
- Research Site
-
Lisboa, Portugal
- Research Site
-
Porto, Portugal
- Research Site
-
Vila Nova de Gaia, Portugal
- Research Site
-
-
-
-
-
Singapore, Singapore
- Research Site
-
-
-
-
-
A Coruña, Spania
- Research Site
-
Alicante, Spania
- Research Site
-
Madrid, Spania
- Research Site
-
Málaga, Spania
- Research Site
-
Zaragoza, Spania
- Research Site
-
-
-
-
-
Chiang Mai, Thailand
- Research Site
-
-
-
-
-
Ankara, Tyrkia
- Research Site
-
Istanbul, Tyrkia
- Research Site
-
Izmir, Tyrkia
- Research Site
-
-
-
-
-
Bad Berka, Tyskland
- Research Site
-
Berlin, Tyskland
- Research Site
-
Essen, Tyskland
- Research Site
-
Großhansdorf, Tyskland
- Research Site
-
Halle, Tyskland
- Research Site
-
Hamburg, Tyskland
- Research Site
-
Heidelberg, Tyskland
- Research Site
-
Köln, Tyskland
- Research Site
-
Oldenburg, Tyskland
- Research Site
-
Ulm, Tyskland
- Research Site
-
Wiesbaden, Tyskland
- Research Site
-
-
-
-
-
Hanoi city, Vietnam
- Research Site
-
Ho Chi Minh city, Vietnam
- Research Site
-
-
-
-
-
Graz, Østerrike
- Research Site
-
Grimmenstein, Østerrike
- Research Site
-
Innsbruck, Østerrike
- Research Site
-
Linz, Østerrike
- Research Site
-
Wels, Østerrike
- Research Site
-
Wien, Østerrike
- Research Site
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 2
Vandetanib + Docetaxel
|
infusion
Andre navn:
oral
Andre navn:
|
|
Aktiv komparator: 1
Docetaxel monotherapy
|
infusion
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Progression-Free Survival (PFS) in the Overall Population
Tidsramme: 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
|
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.
|
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
|
|
Progression-Free Survival (PFS) in the Female Population
Tidsramme: 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
|
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.
|
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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Overall Survival (OS) in the Overall Population
Tidsramme: Time to death in months
|
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).
|
Time to death in months
|
|
Overall Survival (OS) in the Female Population
Tidsramme: Time to death in months
|
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).
|
Time to death in months
|
|
Objective Response Rate (ORR)
Tidsramme: 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
|
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.
|
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
|
|
Disease Control Rate (DCR)
Tidsramme: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
|
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.
|
RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
|
|
Duration of Response (DoR)
Tidsramme: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
|
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)
|
RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
|
|
Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
Tidsramme: FACT-L questionnaires are to be administered every 3 weeks after randomisation
|
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
|
|
Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
Tidsramme: FACT-L questionnaires are to be administered every 3 weeks after randomisation
|
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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Etterforskere
- Studieleder: Contact-US@sanofi.com, Sanofi
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Generelle publikasjoner
- 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.
Hjelpsomme linker
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. mai 2006
Primær fullføring (Faktiske)
1. august 2008
Studiet fullført (Faktiske)
1. mars 2014
Datoer for studieregistrering
Først innsendt
6. april 2006
Først innsendt som oppfylte QC-kriteriene
6. april 2006
Først lagt ut (Anslag)
10. april 2006
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
30. september 2016
Siste oppdatering sendt inn som oppfylte QC-kriteriene
24. august 2016
Sist bekreftet
1. august 2016
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i luftveiene
- Neoplasmer
- Lungesykdommer
- Neoplasmer etter nettsted
- Neoplasmer i luftveiene
- Thoracale neoplasmer
- Karsinom, bronkogent
- Bronkiale neoplasmer
- Lungeneoplasmer
- Karsinom, ikke-småcellet lunge
- Molekylære mekanismer for farmakologisk virkning
- Antineoplastiske midler
- Tubulin modulatorer
- Antimitotiske midler
- Mitosemodulatorer
- Docetaxel
Andre studie-ID-numre
- D4200C00032
- 6474IL/0032
- 2005-004749-32 (EudraCT-nummer)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .