Pharmacogenomic Study for Providing Personalized Strategy to the Treatment of Non-small Cell Lung Cancer (NSCLC) IIIB/IV

Phase 2

Completed

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: IP; Drug: GP

• Registration Number: NCT01003964
• Lead Sponsor: National Cancer Center, Korea

Brief Summary

The primary objective of this randomized phase II study is to compare the Response Rate of each sequence of treatment approach in patients with advanced NSCLC. Additionally, development of gene expression profiles and genotypes that can predict response to commonly used chemotherapy may provide a unique opportunity to better utilize drugs shown to be effective in first- or second-line therapy. Here, the investigators will conduct a pharmacogenomic study to provide rational approach to the treatment of NSCLC by developing predictors of cisplatin (first-line agent) and pemetrexed or docetaxel (second-line agents) sensitivity and demonstrating the clinical value of identifying the most appropriate drug on the basis of sensitivity profile for the treatment regimen of each individual patient. Such an approach is likely to maximize response to chemotherapy and may change the current empirical paradigm of NSCLC therapy.

Detailed Description

Cisplatin-based chemotherapy is currently considered to be the standard treatment in advanced non-small cell lung cancer (NSCLC). However, overall response is only 30-40%, suggesting that a majority of the patients do not respond to platinum. Subsequently, those patients who experience treatment failure with platinum-based therapy typically received pemetrexed or docetaxel as second-line treatment, with response rate of approximately 7% to 10%. The primary objective of this randomized phase II study is to compare the Response Rate of each sequence of treatment approach in patients with advanced NSCLC. Additionally, development of gene expression profiles and genotypes that can predict response to commonly used chemotherapy may provide a unique opportunity to better utilize drugs shown to be effective in first- or second-line therapy. Here, we will conduct a pharmacogenomic study to provide rational approach to the treatment of NSCLC by developing predictors of cisplatin (first-line agent) and pemetrexed or docetaxel (second-line agents) sensitivity and demonstrating the clinical value of identifying the most appropriate drug on the basis of sensitivity profile for the treatment regimen of each individual patient. Such an approach is likely to maximize response to chemotherapy and may change the current empirical paradigm of NSCLC therapy.

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-10-28
• Study First Submitted QC: 2009-10-28
• Study First Posted: 2009-10-29
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-04
• Last Update Posted: 2022-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 289

Inclusion Criteria

• Histologic diagnosis of NSCLC, Stage IV or selected stage IIIB (malignant pleural or pericardial effusion or supraclavicular adenopathy) according to the American Joint Committee on Cancer (AJCC).
• Adequate tumor tissues for ERCC1 analysis.
• No prior chemotherapy.
• Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
• No other forms of cancer therapy, such as radiation, immunotherapy and major surgery for at least 3 weeks before the enrollment in study.
• Performance status of 0, 1, or 2 on the ECOG criteria.
• Measurable disease, according to the Response Evaluation Criteria in Solid Tumors(RECIST), the presence of at least one unidimensionally measurable lesion with longest diameter 10mm by spiral CT scan.
• Estimated life expectancy of at least 12 weeks.
• Patient compliance that allow adequate follow-up.
• Adequate hematologic and renal function.
• Informed consent from patient or patient's relative.
• Males or females at least 18 years of age.
• No pregnancy or breast feeding.
• Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs

Exclusion Criteria

• MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia.
• Serious concomitant infection.
• Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IP group	IP	Irinotecan (65 mg/m2) IV on day1 , 8 Cisplatin (30 mg/m2) IV on day 1 , 8 every 3 weeks
GP group	GP	Gemcitabine (1250 mg/m2) IV on D 1, 8. Cisplatin (75 mg/m2) IV on D1 every 3 weeks.

Primary Outcome Measures

Name	Time	Method
Response Rate	every 6 weeks

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	every 8 weeks	from the first day of treatment to death
Progression-free survival (PFS)	every 6 weeeks	as the period between the day of the treatment and the date of progression or death
adverse event	every 3 weeks	from C1D1 to 30 days after the last dose administration
Pharmacogenomic study using tumor tissue and blood for providing rational strategy to the treatment of advanced NSCLC	2 times	at baseline and time to disease progression

Trial Locations

Locations (1)

National Cancer Center, Korea; 🇰🇷 Goyang-si, Gyeonggi-do, Korea, Republic of