Clinical trial NCT01003964: Pharmacogenomic Study for Providing Personalized Strategy to the Treatment of Non-small Cell Lung Cancer (NSCLC) IIIB/IV
Official title: Randomized phase2 Study of IP vs. GP as the First-line Therapy Followed by Two Different Sequences as the 2nd or 3rd-line Therapy for Patients With Advanced NSCLC;
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: NON-SMALL CELL LUNG CANCER
excision repair cross-complementing 1
Gemcitabine and cisplatin
Irinotecan and cisplatin
advanced NSCLC
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
First posted: 2009-10-29
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Response Rate
timeFrame: every 6 weeks
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: every 8 weeks
measure: Progression-free survival (PFS)
timeFrame: every 6 weeeks
measure: adverse event
timeFrame: every 3 weeks
measure: Pharmacogenomic study using tumor tissue and blood for providing rational strategy to the treatment of advanced NSCLC
timeFrame: 2 times
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center, Korea
state: Gyeonggi-do
Study officials:
affiliation: National Cancer Center
name: JI-YOUN HAN, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Han JY, Choi JJ, Kim JY, Han YL, Lee GK. PNA clamping-assisted fluorescence melting curve analysis for detecting EGFR and KRAS mutations in the circulating tumor DNA of patients with advanced non-small cell lung cancer. BMC Cancer. 2016 Aug 12;16:627. doi: 10.1186/s12885-016-2678-2.