Circulating Tumor DNA (ctDNA) as a Prognostic Tool in Patients With Advanced Lung Adenocarcinoma

NCT03090815 | Unknown

• 1 other identifier: HKU_UW_16_104
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Adenocarcinoma of Lung (Disorder)

Keywords

Circulating Tumor DNA; Prognostic; Molecular tests

Outcome Measures

Primary Outcomes (2)

• ctDNA mutation

  Types of ctDNA mutations

  an average of one year

• Any new ctDNA mutations

  Types of new ctDNA mutations

  an average of one year

Secondary Outcomes (2)

• ctDNA levels [measured as copy number]

  an average of one year

• Any new ctDNA levels [measured as copy number]

  an average of one year

Study Arms (3)

Patient receiving TKI

Patients are diagnosed with primary adenocarcinoma and have no concurrent cancers and are going to receive TKI

Genetic: Sequencing of ctDNA in plasma

Patient receiving ALK-TKI

Patients are diagnosed with primary adenocarcinoma and have no concurrent cancers and are going to receive ALK-TKI

Genetic: Sequencing of ctDNA in plasma

Patient receiving chemotherapy

Patients are diagnosed with primary adenocarcinoma and have no concurrent cancers and are going to receive chemotherapy

Genetic: Sequencing of ctDNA in plasma

Interventions

Sequencing of ctDNA in plasma GENETIC

Sequencing of ctDNA in plasma

Patient receiving ALK-TKI; Patient receiving TKI; Patient receiving chemotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects who are admitted to ward or attended to clinic with confirmed advanced lung adenocarcinoma and planning to receive TKI or chemo as first-line therapy, will be invited to consent for the collection of clinical samples and data and follow-up.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead
• Feinstein Institute for Medical Research: collaborator

Study Sites (1)

University of Hong Kong Queen Mary Hospital

Hong Kong, Hong Kong, 0, Hong Kong

RECRUITING

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Related Links

• Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute, 2013.
• Leading cancer sites in Hong Kong in 2012. Hospital Authority, 2012.

MeSH Terms

Conditions

Adenocarcinoma of Lung

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: March 27, 2017
• Study Start: February 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 27, 2017

Record last verified: 2017-03

Locations

HK (1)