Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Recurrence

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Bevacizumab

Albumin-Bound Paclitaxel

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

bevacizumab 7.5mg/kg+paclitaxel 200mg/m2＋carboplatin area under curve(AUC)=6, every 3 weeks，maximum 4 cycles

Hao Long, Prof

Epidermal growth factor receptor (EGFR) tyrosine kinase is one of most popular target molecules in the field of anticancer drug research. EGFR is highly expressed in many types of tumor cells, which could activate EGFR cytosolic kinase activity by binding to its ligand EGF, and regulates gene expression, cell proliferation, differentiation, apoptosis through different signal transduction pathways. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), competitive to specifically combined with the EGFR kinase domain, thus inhibits its kinase activity, thereby blocking cancer cell proliferation or metastasis. At present, EGFR-TKI has been widely used in clinical activity, especially in patients with EGFR mutations, which had been proved to achieved a certain effect. But with the passage of time, a drug resistance is inevitable.

At present, studies have found that the cessation of treatment immediately after EGFR-TKI resistance may lead to rapid progress of cancer. Chemotherapy, as one of the most widely accepted modality in cancer treatment, might also be one of the salvage therapies of target treatment. Therefore, in patients with better physical status (PS) scores, chemotherapy is commonly applicable.

In January 2010, a study published in the journal of Clinical Lung Cancer reported the application of chemotherapy as salvage treatment for advanced non-small cell lung cancer (NSCLC) patients with resistant to first-line EGFR-TKI treatment. Of the 114 patients enrolled, 67 received sequential chemotherapy, the other 47 patients received best supportive care. The results showed that, sequential chemotherapy can improve the survival time of the patients, compared with chemotherapy and supportive care groups (11.2 months vs. 3.8 months, P\< 0.01). Furthermore, in those who received sequential chemotherapy, a regimen containing paclitaxel got higher efficiency and disease control rate than those without (48.7% vs. 21.4%, 79.5% vs. 53.5% , P\< 0.05), as well as longer progression-free survival (PFS, 5.1 months vs. 1.8 months, P\< 0.01) and overall survival (OS, 12.7 months vs. 7 months, P\< 0.01).

Another study in Taiwan which enrolled 195 patients treated with at least 1 cycles sequential chemotherapy after first-line gefitinib shown similar results. Generally, gefitinib as a first-line treatment had PFS for 5 months, and the second-line treatment efficiency was 14.4%. Regimens of platinum or paclitaxel had a better treatment efficiency (50.6%). A poor therapeutic effect was reported for gefitinib as second-line therapy (5.6%). In total, the median OS of second-line treatment was 12.2 months. In addition, platinum containing regimens survival better (21.7 months vs. 8.9 months, P\< 0.01); patients with mutant EGFR benefit more in a platinum-based chemotherapy (24.5 months vs. 8.5 months, P\< 0.05).

Bevacizumab (trade name Avastin ®) is a kind of recombinant humanized monoclonal immunoglobulin gamma-1 (IgG1) antibody, which can selectively inhibit the combination process of vascular endothelial growth factor (VEGF) and its receptor, Flt-1 and kinase domain receptor (KDR) in endothelial cells. A reduction of tumor angiogenesis, blood supply, oxygen and other nutrients supply could be obtained after the VEGF loss of its biological activity, thus inhibit tumor growth. The drug was approved for the first-line treatment of advanced colorectal cancer in 2004 by America food and Drug Administration (FDA),thus became the first for clinical use of drugs that targeting VEGF. As the first globally approved anti-angiogenic monoclonal antibody drugs, bevacizumab has approved for advanced colorectal cancer, lung cancer, breast cancer, renal cell carcinoma and malignant glioma patients, which was used in more than 500000 cases. In the field of advanced NSCLC treatment, clinical results confirm bevacizumab combined with chemotherapy can prolong OS and PFS of patients with NSCLC, and well tolerated.

The thirty-fifth annual meeting of the European Society of Medical Oncology (ESMO) conference released a meta analysis results of bevacizumab combined with platinum chemotherapy for first-line treatment of advanced non squamous NSCLC. It is confirmed that, treatment with bevacizumab based chemotherapy for advanced non squamous NSCLC patients could achieve significant survival benefit, prolong remission time, and expected safety.

Therefore, the investigators design this phase II to testify the efficacy and safety of bevacizumab + chemotherapy for EGFR-TKI resistant non squamous NSCLC.

Efficacy and Safety Study of Bevacizumab Plus Chemotherapy in EGFR-TKI Resistant Non-Squamous Non-Small Cell Lung Cancer

An Open-labeled, Single Arm, Multicenter Phase II Study to Evaluate Efficacy and Safety of Bevacizumab Plus Chemotherapy for Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer With EGFR-TKI Resistance

Patients were imaged with computed tomography (CT) scan

First Affiliated Hospital, Sun Yat-Sen University

Second Affiliated Hospital, Sun Yat-Sen University

Sun Yat-sen University

Professor

Micronutrients

Hematinics

Vitamins

Pemetrexed

Mitogens

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

1. Chemotherapy regime: Pemetrexed (500mg/m2) + Carboplatin (AUC=5), 1 cycle every 3 weeks, maximum 4 cycles;
2. Intermittent regime: Icotinib 125mg, three times a day, d2-15 in each cycle; maintenance regime: icotinib 125mg, three times a day, since the last cycle until disease progression.

Single drug: Icotinib 125mg, three times a day, continous until disease progression

Pemetrexed (500mg/m2) + Carboplatin (AUC=5), every 3 weeks, maximum 4 cycles; icotinib 125mg, three times a day, d2-15 in each cycle, and icotinib 125mg,three times a day, since the last cycle until disease progression

Icotinib,Pemetrexed,Carboplatin

Single drug: Icotinib 125mg, three times a day, continuous until disease progression.

Icotinib

Ruping Xing

Long Hao, Prof

EGFR-tyrosine kinase inhibitor(TKI)- ie, erlotinib, gefitinib, icotinib,has been recommended as the first option for EGFR-mutated IIIb/IV NSCLC by serial trials as it prolonged patients' progression-free survival. The OPTIMAl trial indicated that those who received TKI and chemotherapy during the whole treatment window survived longest. Unfortunately, previous studies(INTACT, TRIBUTE et al) that concurrently combined TKI and cytotoxic regimens failed to improve survival in unselected patients. To avoid the potential synergistic antagonism, the FAST-ACT II trial committed a sequential strategy and find a superiority in the combination arm upon chemotherapy even in EGFR-mutated group. However, pharmaceutically, the continuous administration of an EGFR-TKI before subsequent chemotherapy in FAST-ACT II could obviate the effects of cytotoxic agents due to the erlotinib-induced G1 arrest.

On the basis of these and other studies, the investigators hypothesized that a better sequential combination strategy of EGFR-TKI and chemotherapy (adding a EGFR-TKI wash-out window before chemotherapy) would be more efficacious than chemotherapy alone. In this study, the investigators investigate the efficacy(PFS:progression free survival), safety, and adverse-event profile of chemotherapy plus intermittent and maintenance of icotinib compared with icotinib single drug, when these drugs were used as first-line treatment in who had non-squamous lung carcinoma with EGFR gene mutation in China.

Intermittent and Maintenance of Icotinib in Combination With Pemetrexed/Carboplatin Compared With Icotinib Single Drug in Ⅲb/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation

A Prospective,Multi-center, Open-labeled Phase 2 Randomized and Comparative Clinical Study of First Line Intermittent and Maintenance of Icotinib in Combination With Pemetrexed/Carboplatin Compared With Icotinib Single Drug in ⅢB/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation

Patients were images with computed tomography (CT) scan

Sun Yat-sen University Cancer Center

Amino Acids

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Pemetrexed 500mg/m2+Carboplatin area under curve(AUC)=5, every 3 weeks, maximum 4 cycles, Erlotinib 150mg/d every cycle d2-15, and Erlotinib 150mg/d from the last cycle until disease progression

150mg po on days 2-15 of each 3 week cycle for 4 cycles and 150mg po per day after 4 cycles until disease progression

Erlotinib

EGFR-tyrosine kinase inhibitor(TKI)- ie, erlotinib, gefitinib, has been recommended as the first option for EGFR-mutated IIIb/IV NSCLC by serial trials as it prolonged patients' progression-free survival. The OPTIMAl trial indicated that those who received TKI and chemotherapy during the whole treatment window survived longest. Unfortunately, previous studies(INTACT, TRIBUTE et al) that concurrently combined TKI and cytotoxic regimens failed to improve survival in unselected patients. To avoid the potential synergistic antagonism, the FAST-ACT II trial committed a sequential strategy and find a superiority in the combination arm upon chemotherapy even in EGFR-mutated group. However, pharmaceutically, the continuous administration of an EGFR-TKI before subsequent chemotherapy in FAST-ACT II could obviate the effects of cytotoxic agents due to the erlotinib-induced G1 arrest.

On the basis of these and other studies, the investigators hypothesized that a better sequential combination strategy of EGFR-TKI and chemotherapy (adding a EGFR-TKI wash-out window before chemotherapy) would be more efficacious than chemotherapy alone. In this study, the investigators investigate the efficacy(PFS:progression free survival), safety, and adverse-event profile of chemotherapy plus intermittent and maintenance of erlotinib, when these drugs were used as first-line treatment in who had non-squamous lung carcinoma with EGFR gene mutation in China.

Intermittent and Maintenance of Erlotinib in Combination With Pemetrexed/Carboplatin in Ⅲb/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation

A Multi-center, Open-labeled Phase 2 Study of First Line Intermittent and Maintenance of Erlotinib in Combination With Pemetrexed/Carboplatin in ⅢB/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety Study of Bevacizumab Plus Chemotherapy in EGFR-TKI Resistant Non-Squamous Non-Small Cell Lung Cancer	NCT02139579	Lung, Carcinoma	Bevacizumab	18 Years - 75 Years	Sun Yat-sen University
Intermittent and Maintenance of Icotinib in Combination With Pemetrexed/Carboplatin Compared With Icotinib Single Drug in Ⅲb/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation	NCT03151161	Lung, Carcinoma	Icotinib,Pemetr... Icotinib	18 Years - 75 Years	Sun Yat-sen University
Intermittent and Maintenance of Erlotinib in Combination With Pemetrexed/Carboplatin in Ⅲb/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation	NCT02066038	Lung, Carcinoma	Erlotinib	18 Years - 75 Years	Sun Yat-sen University
Efficacy and Safety Study of Bevacizumab Plus Chemotherapy in EGFR-TKI Resistant Non-Squamous Non-Small Cell Lung Cancer	NCT02139579	Lung, Carcinoma	Bevacizumab	18 Years - 75 Years	Sun Yat-sen University
Intermittent and Maintenance of Erlotinib in Combination With Pemetrexed/Carboplatin in Ⅲb/IV Non Small Cell Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation	NCT02066038	Lung, Carcinoma	Erlotinib	18 Years - 75 Years	Sun Yat-sen University

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