Clinical trial NCT00509366
Conditions: Non Small Cell Lung Cancer
Keywords: genomics genomics predictor genomics analysis squamous non-squamous
Sponsor: Duke University
Start date: 2007-05-01; Completion date: 2011-12-01
Enrollment: 101 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
In this trial, subjects with chemo-naive advanced non-small cell lung cancer (NSCLC) were assigned to chemotherapy using a genomic-based predictor for platinum sensitivity. After an amendment dated 1/25/2010, subjects with squamous cell NSCLC sensitive to cisplatin received cisplatin/gemcitabine and if resistant to cisplatin received docetaxel/gemcitabine. Subjects with non-squamous cell NSCLC sensitive to cisplatin received cisplatin/pemetrexed and if resistant to cisplatin received pemetrexed/gemcitabine. The primary objective of this trial was to prospectively validate the genomic-based prediction model through separate evaluation of the one-year progression-free survival (PFS) of the cisplatin-sensitive and cisplatin-resistant cohorts. Secondary objectives included: assessment of overall time to progressive disease, quality of life and evaluation of drug sensitivity patterns of cisplatin and pemetrexed.

Detailed description:
Lung cancer is the leading cause of cancer death in both men and women. The majority of patients with lung cancer have non-small cell type (NSCLC). The current standard of care for treating select stage IIIB and stage IV NSCLC is a doublet chemotherapy regimen, such as cisplatin plus gemcitabine, carboplatin plus paclitaxel, or a platinum agent plus vinorelbine. All of these regimens have comparable response rates as first-line therapy. In addition, the combination of cisplatin plus pemetrexed has recently been approved for non-squamous histology, based on results of a large randomized prospective trial in advanced stage NSCLC. Alternative doublet therapy for first-line treatment of NSCLC per ASCO and NCCN guidelines also include a non-platinum doublet or single agent therapy.

An individual patient's response to chemotherapy is the result of complex interactions between the drug(s) and the patient's genetics and environment. Using Affymetrix gene expression data with corresponding drug response data for cisplatin from the NCI60 lines panel, a gene expression based model predicative of cisplatin-resistant has been developed. However, reevaluation of the genomics-based prediction model showed that it was irreproducible, suggesting inaccurate patient assignments into the two cisplatin cohorts. As a result, it would be inappropriate to separately analyze outcomes for the different treatment groups. Instead, information from both cisplatin cohorts will be combined to reflect the overall measure of one-year progression-free survival in this study. Secondary outcomes will also reflect the overall measures of median time to disease progression and quality of life.

Arms: arm 1: Assignment to Treatment Group based on histology and tumor genomics analysis:

Squamous Cell NSCLC-Cisplatin day 1, Gemcitabine days 1 \& 8 Non-Squamous Cell NSCLC-Cisplatin day 1, Pemetrexed day 1

Per an amendment dated 1/25/2010, post-amendment treatment assignment refers to the further separation of patients into sub-groups, within the cisplatin sensitive arm, based on histology (squamous/non-squamous). arm 2: Assignment to Treatment Group based on histology and tumor genomics analysis:

Squamous Cell NSCLC-Docetaxel day 1, Gemcitabine days 1 \& 8 Non-Squamous Cell NSCLC-Pemetrexed day 1, Gemcitabine days 1 \& 8

Per an amendment dated 1/25/2010, post-amendment treatment assignment refers to the further separation of patients into sub-groups, within the cisplatin resistant arm, based on histology (squamous/non-squamous). arm 3: Assignment to Treatment Group based on tumor genomics analysis:

Cisplatin day 1, Gemcitabine days 1 \& 8 arm 4: Assignment to Treatment Group based on tumor genomics analysis:

Pemetrexed day 1, Gemcitabine days 1 \& 8
Interventions: intervention 1: Cisplatin & Gemcitabine intervention 2: Cisplatin & Pemetrexed intervention 3: Docetaxel & Gemcitabine intervention 4: Pemetrexed & Gemcitabine
Intervention descriptions: intervention 1: Squamous Cell NSCLC:

Gemcitabine 1250 mg/m2 IV over 30 minutes day 1 and 8, followed by Cisplatin 75 mg/m2 IV over 60 minutes day 1; repeat every 21 days for up to 6 cycles intervention 2: Non-Squamous Cell NSCLC:

Pemetrexed 500 mg/m2 IV over approximately 10 minutes day 1, followed by Cisplatin 75 mg/m2 IV over 60 minutes day 1; repeat every 21 days for up to 6 cycles intervention 3: Squamous Cell NSCLC:

Docetaxel 75 mg/m2 IV over 60 minutes day 1, followed by Gemcitabine 1250 mg/m2 IV over 30-60 minutes day 1 and alone day 8; repeat every 21 days for up to 6 cycles intervention 4: Non-Squamous Cell NSCLC:

Pemetrexed 500 mg/m2 IV over approximately 10 minutes day 1, followed by Gemcitabine 1250 mg/m2 IV over 30-60 minutes day 1 and alone day 8; repeat every 21 days for up to 6 cycles

Protocol documents: