- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT01936571
Usefulness of Blood Biomarkers for Overall Survival in NSCLC
Use of Blood Biomarkers to Predict Overall Survival for Non-Small-cell Lung Cancer (NSCLC) Patients Treated With (Chemo)Radiotherapy.
Lung cancer is the most common cancer type worldwide, with more than 1.1 million annual deaths. There are two types of the disease, namely non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), with the first accounting for 85% of the total number of cases. The 5-year survival across stages remains disappointingly low, around 10% in most countries, due to a high incidence of both loco-regional and distant failure [3]. However, during the last decade improved radiotherapy techniques allowed an increase of the radiation dose, while at the same time more effective chemo radiation schemes are being applied. These developments have lead to improved outcome in terms of survival. As the TNM staging system is highly inaccurate for the prediction of survival outcome for non-surgical patients, attempts have been made to develop a more accurate risk stratification for these patients [1,2]. A model based on clinical variables yielded an AUC of 0.74, which was encouraging, but also left room for improvement [2]. An extended model, which included clinical as well as biomarker variables, reached a higher AUC, but the limited number of patients included in this study made it impossible to draw definitive conclusions [1].
New prognostic parameters can be retrieved from several sources, which include anatomic, molecular and functional imaging, genomics, proteomics and clinical analysis of patients. The unlimited amount of information is expected to lead to more accurate predictions of individual treatment outcome [4].
The analysis of biomarkers, including proteins, is a fast developing, promising and challenging area of research. Biomarkers can measure or evaluate normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Oncoproteins are produced by, or in response to tumor cells, and may be secreted in the circulation of patients. As tissue sampling is often not possible in lung cancer patients, blood sample collection by venepuncture offers an attractive alternative, which is safe and easy to implement. A number of studies described the prognostic and predictive value of blood biomarkers for NSCLC [5-7]. In this study we will investigate the prognostic value of blood biomarkers related to 1) hypoxia: Osteopontin (OPN), carbonic anhydrase IX (CA-9), and lactate dehydrogenase (LDH); 2) inflammation - interleukin 6 (IL-6), IL-8, and C-reactive protein (CRP), and α-2-macroglobulin (α-2M); and 3) tumor load: Carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA 21-1).
- Dehing-Oberije C, Aerts H, Yu S, De Ruysscher D, Menheere P, Hilvo M, et al. Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):360-368.
- Dehing-Oberije C, Yu S, De Ruysscher D, Meersschout S, Van Beek K, Lievens Y, et al. Development and external validation of prognostic model for 2-year survival of non-small-cell lung cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2009 Jun 1;74(2):355-362.
- Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Paul Kleihues MD, Leslie H. Sobin MD, editors. Lyon, France: IARC Press, International Agency for Research on Cancer; 2004.
- Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P, et al. Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012 Mar;48(4):441-446.
- Donati V, Boldrini L, Dell'Omodarme M, Prati MC, Faviana P, Camacci T, et al. Osteopontin expression and prognostic significance in non-small cell lung cancer. Clin Cancer Res. 2005 Sep 15;11(18):6459-6465.
- Muley T, Fetz TH, Dienemann H, Hoffmann H, Herth FJ, Meister M, et al. Tumor volume and tumor marker index based on CYFRA 21-1 and CEA are strong prognostic factors in operated early stage NSCLC. Lung Cancer. 2008 Jun;60(3):408-415.
- Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, et al. Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Cancer Inst. 2011 Jul 20;103(14):1112-1122.
Tutkimuksen yleiskatsaus
Yksityiskohtainen kuvaus
Lung cancer is the most common cancer type worldwide, with more than 1.1 million annual deaths. There are two types of the disease, namely non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), with the first accounting for 85% of the total number of cases. The 5-year survival across stages remains disappointingly low, around 10% in most countries, due to a high incidence of both loco-regional and distant failure [3]. However, during the last decade improved radiotherapy techniques allowed an increase of the radiation dose, while at the same time more effective chemo radiation schemes are being applied. These developments have lead to improved outcome in terms of survival. As the TNM staging system is highly inaccurate for the prediction of survival outcome for non-surgical patients, attempts have been made to develop a more accurate risk stratification for these patients [1,2]. A model based on clinical variables yielded an AUC of 0.74, which was encouraging, but also left room for improvement [2]. An extended model, which included clinical as well as biomarker variables, reached a higher AUC, but the limited number of patients included in this study made it impossible to draw definitive conclusions [1].
New prognostic parameters can be retrieved from several sources, which include anatomic, molecular and functional imaging, genomics, proteomics and clinical analysis of patients. The unlimited amount of information is expected to lead to more accurate predictions of individual treatment outcome [4].
The analysis of biomarkers, including proteins, is a fast developing, promising and challenging area of research. Biomarkers can measure or evaluate normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Oncoproteins are produced by, or in response to tumor cells, and may be secreted in the circulation of patients. As tissue sampling is often not possible in lung cancer patients, blood sample collection by venepuncture offers an attractive alternative, which is safe and easy to implement. A number of studies described the prognostic and predictive value of blood biomarkers for NSCLC [5-7]. In this study we will investigate the prognostic value of blood biomarkers related to 1) hypoxia: Osteopontin (OPN), carbonic anhydrase IX (CA-9), and lactate dehydrogenase (LDH); 2) inflammation - interleukin 6 (IL-6), IL-8, and C-reactive protein (CRP), and α-2-macroglobulin (α-2M); and 3) tumor load: Carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA 21-1).
- Dehing-Oberije C, Aerts H, Yu S, De Ruysscher D, Menheere P, Hilvo M, et al. Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):360-368.
- Dehing-Oberije C, Yu S, De Ruysscher D, Meersschout S, Van Beek K, Lievens Y, et al. Development and external validation of prognostic model for 2-year survival of non-small-cell lung cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2009 Jun 1;74(2):355-362.
- Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Paul Kleihues MD, Leslie H. Sobin MD, editors. Lyon, France: IARC Press, International Agency for Research on Cancer; 2004.
- Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P, et al. Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012 Mar;48(4):441-446.
- Donati V, Boldrini L, Dell'Omodarme M, Prati MC, Faviana P, Camacci T, et al. Osteopontin expression and prognostic significance in non-small cell lung cancer. Clin Cancer Res. 2005 Sep 15;11(18):6459-6465.
- Muley T, Fetz TH, Dienemann H, Hoffmann H, Herth FJ, Meister M, et al. Tumor volume and tumor marker index based on CYFRA 21-1 and CEA are strong prognostic factors in operated early stage NSCLC. Lung Cancer. 2008 Jun;60(3):408-415.
- Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, et al. Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Cancer Inst. 2011 Jul 20;103(14):1112-1122.
The investigators hypothesize that:
- Higher levels of blood biomarkers are associated with worse survival
- The biomarker information will improve the performance of prediction models, that were previously developed and validated [1, 2]
- Subgroups of patients can be identified that benefit most in terms of a more accurate prediction of survival when using biomarker information
Measurement procedure: Blood samples, that were collected, processed and stored in the Maastro biobank in a standardized way, will be used to measure CRP, LDH, Osteopontin, CA-9 IL-6, IL-8, CEA, CYFRA 21-1, and α-2M. Clinical data will be retrieved from the electronic medical files.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Yhteystiedot ja paikat
Opiskelupaikat
-
-
Limburg
-
Maastricht, Limburg, Alankomaat, 6229 ET
- Maastro clinic
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Lapsi
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Näytteenottomenetelmä
Tutkimusväestö
Kuvaus
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Havaintomallit: Kohortti
- Aikanäkymät: Tulevaisuuden
Kohortit ja interventiot
Ryhmä/Kohortti |
Interventio / Hoito |
---|---|
NSCLC
The cohort consists of approximately 250 patients.
As a rule of thumb 5-10 events per variable are needed to avoid overfitting a model.
To model 6 clinical variables + 9 biomarker variables 75-150 events are needed.
Assuming a two-year survival of 40%, the calculated (constant) hazard rate is 0.46 per year.
With an inclusion rate of 50 patients per year, and a follow-up time varying between 0.5 and 4 year, at the time of analysis (November/December 2013) it is expected that there will be 138 events available for analysis.
|
Blood samples, that were collected, processed and stored in the Maastro biobank in a standardized way, will be used to measure CRP, LDH, Osteopontin, CA-9 IL-6, IL-8, CEA, CYFRA 21-1, and α-2M.
Clinical data will be retrieved from the electronic medical files.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Aikaikkuna |
---|---|
Correlation of blood biomarkers to overall survival
Aikaikkuna: 4 years
|
4 years
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: Cary Oberije, PhD, Maastro Clinic, The Netherlands
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Arvio)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- Blood Biomarkers
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Yhdysvalloissa valmistettu ja sieltä viety tuote
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .
Kliiniset tutkimukset Ei-pienisoluinen keuhkosyöpä
-
Jonsson Comprehensive Cancer CenterEli Lilly and Company; Genentech, Inc.RekrytointiMetastaattinen keuhkojen ei-pienisolusyöpä | Tulenkestävä keuhkojen ei-pienisolusyöpä | Stage IV Lung Cancer American Joint Committee on Cancer (AJCC) v8 | Stage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8Yhdysvallat
-
University of Southern CaliforniaNational Cancer Institute (NCI); Genentech, Inc.RekrytointiStage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | Keuhkojen ei-pienisolukarsinooma | Vaiheen III keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8 | Vaiheen II keuhkosyöpä AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Vaiheen IIB keuhkosyöpä AJCC v8 | Vaiheen IIIA keuhkosyöpä AJCC v8 | Vaiheen IIIB... ja muut ehdotYhdysvallat
-
Eben RosenthalRekrytointiStage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8 | Keuhkokarsinooma | Metastaattinen pahanlaatuinen kasvain keuhkoissaYhdysvallat
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)LopetettuPienisoluinen keuhkosyöpä | Stage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8Yhdysvallat
-
Emory UniversityNational Cancer Institute (NCI)RekrytointiStage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | Keuhkojen ei-pienisolukarsinooma | IV vaiheen keuhkosyöpä AJCC v8Yhdysvallat
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; California Institute... ja muut yhteistyökumppanitRekrytointiStage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | Keuhkojen ei-pienisolukarsinooma | IV vaiheen keuhkosyöpä AJCC v8Yhdysvallat
-
Ohio State University Comprehensive Cancer CenterRekrytointiStage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8 | Keuhkojen ei-squamous ei-pienisolusyöpä | Vaiheen IIIB keuhkosyöpä AJCC v8Yhdysvallat
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Aktiivinen, ei rekrytointiStage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | Vaiheen III keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8 | Vaiheen II keuhkosyöpä AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Vaiheen IIB keuhkosyöpä AJCC v8 | Vaiheen IIIA keuhkosyöpä AJCC v8 | Vaiheen IIIB keuhkosyöpä AJCC v8 | I vaiheen... ja muut ehdotYhdysvallat
-
M.D. Anderson Cancer CenterPeruutettuMetastaattinen keuhkojen ei-pienisolusyöpä | Stage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI)RekrytointiMetastaattinen keuhkojen ei-pienisolusyöpä | Stage IVA Lung Cancer AJCC v8 | Vaihe IVB keuhkosyöpä AJCC v8 | Vaiheen III keuhkosyöpä AJCC v8 | IV vaiheen keuhkosyöpä AJCC v8 | Vaiheen II keuhkosyöpä AJCC v8 | Stage IIA Lung Cancer AJCC v8 | Vaiheen IIB keuhkosyöpä AJCC v8 | Vaiheen IIIA keuhkosyöpä AJCC v8 | Vaiheen... ja muut ehdotYhdysvallat
Kliiniset tutkimukset Blood samples
-
Thomas Jefferson UniversityRekrytointiRelapse Remitting multippeliskleroosiYhdysvallat
-
Natera, Inc.Eunice Kennedy Shriver National Institute of Child Health and Human Development... ja muut yhteistyökumppanitLopetettuAneuploidia | Trisomia 21 | Trisomia 18 | Trisomia 13Yhdysvallat, Irlanti, Kanada, Italia, Korean tasavalta, Espanja
-
University of PittsburghValmis
-
University of California, DavisValmis
-
Ohio State UniversityPeruutettuTerveet yksilötYhdysvallat
-
Children's Hospital Los AngelesRekrytointiLasten kiinteä kasvain, määrittelemätön, protokollakohtainenYhdysvallat
-
Anthony MaglioccoMontefiore Medical Center; University of Saskatchewan; DHR Health Institute... ja muut yhteistyökumppanitRekrytointi
-
Lawson Health Research InstituteUniversity of Toronto; University of Western Ontario, Canada; MOUNT SINAI... ja muut yhteistyökumppanitRekrytointi
-
Intermountain Health Care, Inc.Rekrytointi
-
Abramson Cancer Center of the University of PennsylvaniaPeruutettuVakava tai lievä toksisuus sädehoidosta ja/tai kemoterapiastaYhdysvallat