Therapeutic Resistance Prediction of Tyrosine Kinase Inhibitors

Non-small Cell Lung Cancer Clinical Trial

Official title:

Association of Computed Tomography Phenotypic Signature With Progression-free Survival in Stage IV EGFR-mutant Non-small Cell Lung Cancer Undergoing Tyrosine Kinase Inhibitors

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02851329
• Other study ID #: 20160728TRPN
• Status: Enrolling by invitation
• Phase: N/A
• First received: July 28, 2016
• Last updated: January 17, 2017
• Start date: February 2015
• Est. completion date: July 2017

Study information

• Verified date: January 2017
• Source: Chinese Academy of Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators propose a non-invasive prognostic tool for TKIs resistance in patients with stage IV EGFR-mutant non-small cell lung cancer (NSCLC) by computed tomography phenotypic features, which can be conveniently translated to facilitate the pre-therapy individualized management of EGFR TKIs in this disease.

Description:

The investigators develop a multi-CT-phenotypic-feature-based classifier to predict TKI benefit and therapeutic resistance for stage IV EGFR-mutant non-small cell lung cancer (NSCLC). The investigators also compared its prognostic and predictive efficacy with single features and clinicopathological risk factors. An individualized nomogram integrated the classifier and three clinicopathological risk factors was built for clinical use. The prognostic accuracy of the proposed model was evaluated in two independent validation sets.

Nearly 500 patients will be enrolled in this clinical trial. Eligible patients were diagnosed with NSCLC, and stage IV according to the TNM system classification of the American Joint Committee on Cancer, presence of activating EGFR mutations, age 20 years or older, and no history of systemic anticancer therapy for advanced disease. Patients who underwent first-line or second-line EGFR TKIs were eligible for inclusion. All patients had to be capable of undergoing contrast-enhanced CT, and pretreatment CT was strictly controlled in two weeks before the EGFR TKIs starts. Patients who underwent resection for local advanced or metastatic disease were withdrawn from the study.

Therapeutic resistance was measured by PFS, as the time from the initiation of EGFR TKIs therapy to the date of confirmed disease progression or death. PFS was censored at the date of death from other causes, or the date of the last follow-up visit for progression-free patients.

The investigators will use extracted 1000 phenotypic features on the region of interest manually segmented by radiologists. The Lasso Cox regression model and Nomogram will be used to build a prognosis model for the therapeutic resistance prediction of EGFR TKIs for stage IV EGFR-mutant NSCLC. The Harrell's concordance index(C-index) of the proposed nomogram will be used to quantify the discrimination performance.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 500
• Est. completion date: July 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Eligible patients were diagnosed with NSCLC, and stage IV according to the TNM system classification of the American Joint Committee on Cancer.

• Presence of activating EGFR mutations.

• Age 20 years or older, and no history of systemic anticancer therapy for advanced disease.

• Patients who underwent first-line or second-line EGFR TKIs were eligible for inclusion.

• All patients had to be capable of undergoing contrast-enhanced CT, and pretreatment CT was strictly controlled in two weeks before the EGFR TKIs starts.

Exclusion Criteria:

• Based on the criteria above, patients who underwent resection for local advanced or metastatic disease were withdrawn from the study.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Locations

Country	Name	City	State
China	Key Laboratory of Molecular Imaging, Chinese Academy of Sciences	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Chinese Academy of Sciences	Guangdong Academy of Medical Sciences, Shanghai Pulmonary Hospital, Shanghai, China, West China Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Balachandran VP, Gonen M, Smith JJ, DeMatteo RP. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015 Apr;16(4):e173-80. doi: 10.1016/S1470-2045(14)71116-7. Review. — View Citation

Crystal AS, Shaw AT, Sequist LV, Friboulet L, Niederst MJ, Lockerman EL, Frias RL, Gainor JF, Amzallag A, Greninger P, Lee D, Kalsy A, Gomez-Caraballo M, Elamine L, Howe E, Hur W, Lifshits E, Robinson HE, Katayama R, Faber AC, Awad MM, Ramaswamy S, Mino-Kenudson M, Iafrate AJ, Benes CH, Engelman JA. Patient-derived models of acquired resistance can identify effective drug combinations for cancer. Science. 2014 Dec 19;346(6216):1480-6. doi: 10.1126/science.1254721. — View Citation

Lambin P, van Stiphout RG, Starmans MH, Rios-Velazquez E, Nalbantov G, Aerts HJ, Roelofs E, van Elmpt W, Boutros PC, Granone P, Valentini V, Begg AC, De Ruysscher D, Dekker A. Predicting outcomes in radiation oncology--multifactorial decision support systems. Nat Rev Clin Oncol. 2013 Jan;10(1):27-40. doi: 10.1038/nrclinonc.2012.196. Review. — View Citation

Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Erratum in: Lancet Oncol. 2012 May;13(5):e186. — View Citation

Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival		3 years