Clinical trial NCT01404260
Conditions: Non-small Cell Lung Cancer
Keywords: chemotherapy maintenance therapy gefitinib
Sponsor: Guangdong Association of Clinical Trials
Start date: 2011-06-01; Completion date: 2015-10-01
Enrollment: 219 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Platinum-based combination chemotherapy, such as gemcitabine-carboplatin, is one of the standard first-line therapy for advanced non-small cell lung cancer (NSCLC).

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have clinical efficacy, as compared with the best supportive care or standard chemotherapy, when given as second-line or third-line therapy for advanced NSCLC.

Treatment with EGFR-TKI is most effective in female, never-smoker, or patients with adenocarcinoma, and patients of Asian origin. In these populations, such treatment is associated with favorable objective response rates, progression-free survival, and overall survival. These populations also have a relatively high incidence of somatic mutations in the region of the EGFR gene that encodes the tyrosine kinase domain.

The recent study(IPASS) by Tony S. Mok showed gefitinib was superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia . In the subgroup of 261 patients who were positive for the EGFR gene mutation, PFS was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel(HR= 0.48,P\<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, PFS was significantly longer among those who received carboplatin-paclitaxel(HR=2.85,P\<0.001). Gefitinib treatment was well tolerated, with lower in hematologic toxicity, and no treatment-related interstitial lung disease.In this study(IPASS), only patients with a mutation of the EGFR gene in the tumor could get benefit from gefitinib as first line treatment.

Tony S. Mok and his colleague also found that intercalating and maintenance administration of erlotinib(another EGFR-TKI)following gemcitabine/platinum chemotherapy as first line therapy led to a significant improvement in PFS .

Detailed description:
Nowadays,EGFR mutation status is unknown for most of the advanced NSCLC patients in clinical practice.Those patients with high probability of EGFR mutation maybe could get benefit from gefitinib as first-line treatment. For this reason, the investigators need more investigation to focus on EGFR mutation unknown patients. In the previous study (including FAST-ACT), the patients enrolled trial received EGFR-TKI plus chemotherapy nearly simultaneously,so the investigators could not know whether those patients gained benefit from EGFR-TKI or chemotherapy, maybe chemotherapy alone was enough. If the patients with EGFR mutation status unknown could get stable disease(SD) after two cycles of chemotherapy,those patients may be optimal for the investigation of intercalating and maintenance administration of gefitinib. The reasons are that chemotherapy may be enough for those with objective response after two cycles chemotherapy, of course, those with disease progression (PD) should be excluded from the study.

On the basis of these and other studies, the investigators hypothesized that in a selected population,first-line chemotherapy(gemcitabine +carboplatin) with intercalating and maintenance use of gefitinib would be more efficacious than chemotherapy alone. In this study, the investigators compared the efficacy, safety, and adverse-event profile of chemotherapy plus gefitinib with those of chemotherapy alone, when these drugs were used as first-line treatment in nonsmokers or former light smokers in China, who had lung adenocarcinoma with EGFR gene mutation unknown.

Arms: arm 1: Arm A: Gemcitabine 1250mg/m2+Carboplatin AUC=5, every 4 weeks, maximum 4 cycles, Gefitinib 250mg/d every cycle d15-25, and Gefitinib 250mg/d from d15 of last cycle until disease progression arm 2: Arm B: Gemcitabine 1250mg/m2+Carboplatin AUC=5, every 4 weeks, maximum4 cycles, observation until disease progression
Interventions: intervention 1: Gefitinib intervention 2: Gemcitabine +Carboplatin
Intervention descriptions: intervention 1: Gefitinib 250mg/d every cycle d15-25,and Gefitinib 250mg/d from d15 of last cycle until disease progression intervention 2: Gemcitabine 1250mg/m2+Carboplatin AUC=5, every 4 weeks, maximum 4 cycles

Protocol documents: