Adenocarcinoma of Lung (Disorder) Clinical Trial
Official title:
Circulating Tumor DNA (ctDNA) as a Prognostic Tool in Patients With Advanced Lung Adenocarcinoma
Verified date | March 2017 |
Source | The University of Hong Kong |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational [Patient Registry] |
Lung cancer is the leading cause of cancer death in the U.S. and throughout the world. Lung
cancers are broadly divided histologically into small cell lung cancer (SCLC) and non-small
cell lung cancer (NSCLC). About 25% of patients with NSCLC have stage I or II disease. The
primary treatment modality is surgical resection,2 and 5-year survival rates are 65% for
stage I and 41% for stage II disease. However, more than 70% of patients with NSCLC present
with stage III or IV disease. Patients with stage III disease are most commonly treated with
chemoradiation, and 5-year survival rate is 26%. Chemotherapy and targeted therapy are often
used for stage IV disease, which has a 5-year survival rate of 4%.
Tyrosine kinase inhibitor (TKI) is a targeted therapy against specific molecules in critical
cell-signaling pathways involved in lung carcinogenesis. The currently available FDA
approved TKIs for advanced NSCLC include afatinib, gefitinib, and erlotinib that inhibit
epidermal growth factor receptor (EGFR) signaling 6 and crizotinib that inhibits anaplastic
lymphoma kinase (ALK) signaling. However, only tumors that carry the corresponding oncogenic
mutations (e.g., sensitizing EGFR mutations) would respond well to these TKIs. Meta-analyses
of clinical trials evaluating the efficacy of gefitinib and erlotinib have demonstrated that
NSCLC patients who are EGFR mutation-positive have a lower risk of disease progression when
treated with an EGFR-TKI as compared to those treated with chemotherapy (HR = 0.43, 95%
confidence interval, CI=0.38-0.49). EGFR-TKI, however, confers no benefits to patients who
are EGFR wildtype (HR = 1.06, 95% CI=0.94-1.19). A phase III trial of crizotinib has also
demonstrated the superiority of crizotinib to standard chemotherapy in ALK-positive NSCLC
patients (HR = 0.49; 95% CI=0.37-0.64).
In Hong Kong, as in other parts of Asia like in China and in Taiwan, other than the majority
of lung cancer patients being smokers, there is also a prominence of non-smokers in lung
cancer. Compared with Caucasians, there is also a relatively higher incidence of EGFR
mutation in lung adenocarcinomas. The prevalence of EGFR mutation in Asian population with
lung adenocarcinomas can reach up to 60% compared to at most 30% in the Caucasian
population. These EGFR mutant tumors will demonstrate better response to the drug EGFR-TKI,
boosting up the response rate to almost 70% compared to 30% with conventional chemotherapy
for lung cancer. Even with this remarkable response, however, EGFR-TKI will eventually fail
in EGFR mutant lung cancer. There is an imminent need to look for newer therapeutic targets
or agents that can overcome this acquired resistance to anti-cancer drugs and to explore
alternative molecular signaling pathways that could interact or enhance EGFR signaling
pathways to modulate the therapeutic response in lung cancer.
Status | Recruiting |
Enrollment | 100 |
Est. completion date | December 2017 |
Est. primary completion date | December 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility |
Inclusion Criteria: - Patients are eligible if they (1) are diagnosed with primary adenocarcinoma, (2) have no concurrent cancers, (3) are going to receive TKI or chemo as first-line therapy, and (4) are willing to sign informed consent and enrolled in the study before treatment starts. Exclusion Criteria: - Patients have other concurrent cancers - Patients who are not eligible receive TKI or chemo as first-line therapy - Patients who are not willing or able to sign informed consent - Histology other than adenocarcinoma |
Country | Name | City | State |
---|---|---|---|
Hong Kong | University of Hong Kong Queen Mary Hospital | Hong Kong |
Lead Sponsor | Collaborator |
---|---|
The University of Hong Kong | Feinstein Institute for Medical Research |
Hong Kong,
Antonicelli A, Cafarotti S, Indini A, Galli A, Russo A, Cesario A, Lococo FM, Russo P, Mainini AF, Bonifati LG, Nosotti M, Santambrogio L, Margaritora S, Granone PM, Dutly AE. EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation. Int J Med Sci. 2013;10(3):320-30. doi: 10.7150/ijms.4609. Review. — View Citation
Arcila ME, Oxnard GR, Nafa K, Riely GJ, Solomon SB, Zakowski MF, Kris MG, Pao W, Miller VA, Ladanyi M. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res. 2011 Mar 1;17(5):1169-80. doi: 10.1158/1078-0432.CCR-10-2277. — View Citation
Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094. — View Citation
Cabezón-Gutiérrez L, Khosravi-Shahi P, Diaz-Muñoz-de-la-Espada VM, Carrión-Galindo JR, Eraña-Tomás I, Castro-Otero M. ALK-mutated non-small-cell lung cancer: a new strategy for cancer treatment. Lung. 2012 Aug;190(4):381-8. doi: 10.1007/s00408-012-9391-y. Review. — View Citation
Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013 Mar 28;368(13):1199-209. doi: 10.1056/NEJMoa1213261. — View Citation
Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014 Feb 20;32(6):579-86. doi: 10.1200/JCO.2012.45.2011. Review. — View Citation
Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, Allen B, Bozic I, Reiter JG, Nowak MA, Kinzler KW, Oliner KS, Vogelstein B. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012 Jun 28;486(7404):537-40. doi: 10.1038/nature11219. — View Citation
Freidin MB, Freydina DV, Leung M, Montero Fernandez A, Nicholson AG, Lim E. Circulating tumor DNA outperforms circulating tumor cells for KRAS mutation detection in thoracic malignancies. Clin Chem. 2015 Oct;61(10):1299-304. doi: 10.1373/clinchem.2015.242453. — View Citation
Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakagawa K, Chu DT, Saijo N, Duffield EL, Rukazenkov Y, Speake G, Jiang H, Armour AA, To KF, Yang JC, Mok TS. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011 Jul 20;29(21):2866-74. doi: 10.1200/JCO.2010.33.4235. — View Citation
Gadgeel SM, Ramalingam SS, Kalemkerian GP. Treatment of lung cancer. Radiol Clin North Am. 2012 Sep;50(5):961-74. doi: 10.1016/j.rcl.2012.06.003. Review. — View Citation
Gao G, Ren S, Li A, Xu J, Xu Q, Su C, Guo J, Deng Q, Zhou C. Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials. Int J Cancer. 2012 Sep 1;131(5):E822-9. doi: 10.1002/ijc.27396. — View Citation
Giroux S. Overcoming acquired resistance to kinase inhibition: the cases of EGFR, ALK and BRAF. Bioorg Med Chem Lett. 2013 Jan 15;23(2):394-401. doi: 10.1016/j.bmcl.2012.11.037. Review. — View Citation
Hsu KH, Chen KC, Yang TY, Yeh YC, Chou TY, Chen HY, Tsai CR, Chen CY, Hsu CP, Hsia JY, Chuang CY, Tsai YH, Chen KY, Huang MS, Su WC, Chen YM, Hsiung CA, Chang GC, Chen CJ, Yang PC. Epidermal growth factor receptor mutation status in stage I lung adenocarcinoma with different image patterns. J Thorac Oncol. 2011 Jun;6(6):1066-72. doi: 10.1097/JTO.0b013e31821667b0. — View Citation
Inukai M, Toyooka S, Ito S, Asano H, Ichihara S, Soh J, Suehisa H, Ouchida M, Aoe K, Aoe M, Kiura K, Shimizu N, Date H. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res. 2006 Aug 15;66(16):7854-8. — View Citation
Lam DC, Tam TC, Lau KM, Wong WM, Hui CK, Lam JC, Wang JK, Lui MM, Ho JC, Ip MS. Plasma EGFR Mutation Detection Associated With Survival Outcomes in Advanced-Stage Lung Cancer. Clin Lung Cancer. 2015 Nov;16(6):507-13. doi: 10.1016/j.cllc.2015.06.003. — View Citation
Lee CK, Brown C, Gralla RJ, Hirsh V, Thongprasert S, Tsai CM, Tan EH, Ho JC, Chu da T, Zaatar A, Osorio Sanchez JA, Vu VV, Au JS, Inoue A, Lee SM, Gebski V, Yang JC. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013 May 1;105(9):595-605. doi: 10.1093/jnci/djt072. Review. — View Citation
Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008 Jul 24;359(4):366-77. doi: 10.1056/NEJMoa0800668. — View Citation
Mok T, Wu YL, Lee JS, Yu CJ, Sriuranpong V, Sandoval-Tan J, Ladrera G, Thongprasert S, Srimuninnimit V, Liao M, Zhu Y, Zhou C, Fuerte F, Margono B, Wen W, Tsai J, Truman M, Klughammer B, Shames DS, Wu L. Detection and Dynamic Changes of EGFR Mutations from Circulating Tumor DNA as a Predictor of Survival Outcomes in NSCLC Patients Treated with First-line Intercalated Erlotinib and Chemotherapy. Clin Cancer Res. 2015 Jul 15;21(14):3196-203. doi: 10.1158/1078-0432.CCR-14-2594. — View Citation
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. — View Citation
Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T, Piskorz AM, Parkinson C, Chin SF, Kingsbury Z, Wong AS, Marass F, Humphray S, Hadfield J, Bentley D, Chin TM, Brenton JD, Caldas C, Rosenfeld N. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 2013 May 2;497(7447):108-12. doi: 10.1038/nature12065. — View Citation
Nesbitt JC, Putnam JB Jr, Walsh GL, Roth JA, Mountain CF. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg. 1995 Aug;60(2):466-72. Review. — View Citation
Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, Liu CL, Neal JW, Wakelee HA, Merritt RE, Shrager JB, Loo BW Jr, Alizadeh AA, Diehn M. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014 May;20(5):548-54. doi: 10.1038/nm.3519. — View Citation
Ohashi K, Maruvka YE, Michor F, Pao W. Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J Clin Oncol. 2013 Mar 10;31(8):1070-80. doi: 10.1200/JCO.2012.43.3912. Review. — View Citation
Perkins G, Yap TA, Pope L, Cassidy AM, Dukes JP, Riisnaes R, Massard C, Cassier PA, Miranda S, Clark J, Denholm KA, Thway K, Gonzalez De Castro D, Attard G, Molife LR, Kaye SB, Banerji U, de Bono JS. Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers. PLoS One. 2012;7(11):e47020. doi: 10.1371/journal.pone.0047020. — View Citation
Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med. 2011 Mar 23;3(75):75ra26. doi: 10.1126/scitranslmed.3002003. — View Citation
Shaw AT, Engelman JA. ALK in lung cancer: past, present, and future. J Clin Oncol. 2013 Mar 10;31(8):1105-11. doi: 10.1200/JCO.2012.44.5353. Review. — View Citation
Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. doi: 10.1056/NEJMoa1214886. Erratum in: N Engl J Med. 2015 Oct 15;373(16):1582. — View Citation
Shi Y, Au JS, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, Heeroma K, Itoh Y, Cornelio G, Yang PC. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014 Feb;9(2):154-62. doi: 10.1097/JTO.0000000000000033. — View Citation
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29. doi: 10.3322/caac.20138. — View Citation
Subramanian J, Govindan R. Lung cancer in never smokers: a review. J Clin Oncol. 2007 Feb 10;25(5):561-70. Review. — View Citation
Suda K, Mizuuchi H, Maehara Y, Mitsudomi T. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny. Cancer Metastasis Rev. 2012 Dec;31(3-4):807-14. doi: 10.1007/s10555-012-9391-7. Review. — View Citation
Uchida J, Kato K, Kukita Y, Kumagai T, Nishino K, Daga H, Nagatomo I, Inoue T, Kimura M, Oba S, Ito Y, Takeda K, Imamura F. Diagnostic Accuracy of Noninvasive Genotyping of EGFR in Lung Cancer Patients by Deep Sequencing of Plasma Cell-Free DNA. Clin Chem. 2015 Sep;61(9):1191-6. doi: 10.1373/clinchem.2015.241414. — View Citation
Yam I, Lam DC, Chan K, Chung-Man Ho J, Ip M, Lam WK, Chan TK, Chan V. EGFR array: uses in the detection of plasma EGFR mutations in non-small cell lung cancer patients. J Thorac Oncol. 2012 Jul;7(7):1131-40. doi: 10.1097/JTO.0b013e3182558198. — View Citation
* Note: There are 33 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | ctDNA mutation | Types of ctDNA mutations | an average of one year | |
Primary | Any new ctDNA mutations | Types of new ctDNA mutations | an average of one year | |
Secondary | ctDNA levels [measured as copy number] | Quantity of ctDNA mutations | an average of one year | |
Secondary | Any new ctDNA levels [measured as copy number] | Quantity of new type ctDNA | an average of one year |