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

• ClinicalTrials.gov Identifier: NCT01003964
• Recruitment Status: Unknown
• First Posted: October 29, 2009
• Last Update Posted: November 14, 2013
• Sponsor: National Cancer Center, Korea
• Information provided by (Responsible Party): Ji-youn Han, National Cancer Center, Korea

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Irinotecan, Cisplatin, Gemcitabine, Pemetrexed, Docetaxel	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 284 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: February 2009
• Estimated Primary Completion Date: September 2014
• Estimated Study Completion Date: December 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: ERCC1 negative - GP; Gemcitabine (1250 mg/m2) IV on D 1, 8. Cisplatin (75 mg/m2) IV on D1 every 3 weeks.	Drug: Irinotecan, Cisplatin, Gemcitabine, Pemetrexed, Docetaxel; GP: Gemcitabine (1250 mg/m2) IV on day1, 8. Cisplatin (75 mg/m2) IV on day1 every 3 weeks IP: Irinotecan (65 mg/m2) IV on day 1 , 8 Cisplatin (30 mg/m2) IV on day 1 , 8 every 3 weeks 2nd or 3rd: Pemetrexed (500 mg/m2) D1 with premedication every 3 weeks Docetaxel (75 mg/m2) D1 with premedication every 3 weeks; Other Name: Campto
Experimental: ERCC1 positive - IP; Irinotecan (65 mg/m2) IV on day1 , 8 Cisplatin (30 mg/m2) IV on day 1 , 8 every 3 weeks	Drug: Irinotecan, Cisplatin, Gemcitabine, Pemetrexed, Docetaxel; GP: Gemcitabine (1250 mg/m2) IV on day1, 8. Cisplatin (75 mg/m2) IV on day1 every 3 weeks IP: Irinotecan (65 mg/m2) IV on day 1 , 8 Cisplatin (30 mg/m2) IV on day 1 , 8 every 3 weeks 2nd or 3rd: Pemetrexed (500 mg/m2) D1 with premedication every 3 weeks Docetaxel (75 mg/m2) D1 with premedication every 3 weeks; Other Name: Campto
Experimental: ERCC1 positive - GP; Gemcitabine (1250 mg/m2) IV on day1, 8 Cisplatin (75 mg/m2) IV on day1 every 3 weeks	Drug: Irinotecan, Cisplatin, Gemcitabine, Pemetrexed, Docetaxel; GP: Gemcitabine (1250 mg/m2) IV on day1, 8. Cisplatin (75 mg/m2) IV on day1 every 3 weeks IP: Irinotecan (65 mg/m2) IV on day 1 , 8 Cisplatin (30 mg/m2) IV on day 1 , 8 every 3 weeks 2nd or 3rd: Pemetrexed (500 mg/m2) D1 with premedication every 3 weeks Docetaxel (75 mg/m2) D1 with premedication every 3 weeks; Other Name: Campto
Experimental: ERCC1 negative - IP; Irinotecan (65 mg/m2) IV on day1, 8 Cisplatin (30 mg/m2) IV on day 1, 8 every 3 weeks	Drug: Irinotecan, Cisplatin, Gemcitabine, Pemetrexed, Docetaxel; GP: Gemcitabine (1250 mg/m2) IV on day1, 8. Cisplatin (75 mg/m2) IV on day1 every 3 weeks IP: Irinotecan (65 mg/m2) IV on day 1 , 8 Cisplatin (30 mg/m2) IV on day 1 , 8 every 3 weeks 2nd or 3rd: Pemetrexed (500 mg/m2) D1 with premedication every 3 weeks Docetaxel (75 mg/m2) D1 with premedication every 3 weeks; Other Name: Campto

Outcome Measures

Primary Outcome Measures :

1. Response Rate [ Time Frame: every 6 weeks ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

Korea, Republic of

National Cancer Center, Korea

Goyang-si, Gyeonggi-do, Korea, Republic of

Sponsors and Collaborators

National Cancer Center, Korea

Investigators

• Principal Investigator: JI-YOUN HAN, M.D.; National Cancer Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum in: BMC Cancer. 2016 Oct 17;16(1):803.

• Responsible Party: Ji-youn Han, Head, Center for Lung Cancer, National Cancer Center, Korea
• ClinicalTrials.gov Identifier: NCT01003964
• Other Study ID Numbers: NCCCTS-08-371
• First Posted: October 29, 2009
• Last Update Posted: November 14, 2013
• Last Verified: November 2013

Keywords provided by Ji-youn Han, National Cancer Center, Korea:

NON-SMALL CELL LUNG CANCER; excision repair cross-complementing 1; Gemcitabine and cisplatin; Irinotecan and cisplatin; Pemetrexed; Docetaxel; advanced NSCLC

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Gemcitabine; Docetaxel; Irinotecan; Pemetrexed; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Folic Acid Antagonists