Icotinib With Concurrent Radiotherapy vs. Chemoradiotherapy in Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The current standard of care for unresectable locally advanced non-small-cell lung cancer (NSCLC) is a combination of chemotherapy and thoracic radiotherapy (TRT). The standard regimens consist of platinum-based doublet chemotherapy.Icotinib(BPI-2009, Conmana) is the first self-developed small molecular drug in China for targeted therapy of lung cancer.Icotinib is a novel oral quinazoline compound that has proven survival benefit in Chinese patients with lung cancer,especially in EGFR mutation lung cancer. This randomised, multi-center, controlled trial is designed to assess the efficacy and safety of icotinib with concurrent radiotherapy versus pemetrexed + carboplatin with concurrent radiotherapy in inoperable stage III non-small cell lung cancer with EGFR mutation, the primary endpoint is progression-free survival.

Official Title
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A Phase 2 Study of Icotinib With Concurrent Radiotherapy vs. Pemetrexed+ Carboplatin With Concurrent Radiotherapy in Unresectable Stage III Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor ( EGFR) Mutation

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Icotinib
* Drug: Pemetrexed
* Drug: Carboplatin
* Radiation: Thoracic radiotherapy(TRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable stage IIIA / IIIB non-small cell lung cancer with EGFR 19/21 mutation. No previous systemic anticancer therapy. life expectancy more than three months. ECOG Performance Status of 0 to 1. Measurable lesion according to RECIST with at least one measurable lesion not previously irradiated, unless disease progression has been documented at that site. Patients will be required to provide informed consent before enrollment. Exclusion Criteria: Intrapulmonary metastasis, atelectasis of an entire hemithorax,pleural dissemination, or contralateral hilar lymph node metastasis. Prior chemotherapy for NSCLC, chest irradiation therapy, or therapy directed at the epidermal growth factor receptor pathway. Severe heart disease, uncontrolled diabetes mellitus, or active infection. Active concomitant malignancy, and pregnancy or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Icotinib with concurrent radiotherapy<br>Icotinib (125 mg ,three times daily)with concurrent thoracic radiotherapy(TRT) (66 Gy/33 fractions), followed by maintenance icotinib (125 mg ,Three times daily) until disease progression or unacceptable toxicity. | Drug: Icotinib<br>* Icotinib (125 mg ,Three times daily)<br>* Other names: Conmana;Radiation: Thoracic radiotherapy(TRT)<br>* TRT (total dose 66Gy, 2Gy per time, once a day, five times a week, a total of 33 times)<br>|
| Active Comparator: Chemoradiotherapy<br>Pemetrexed(500mg/m2) + carboplatin (AUC，5) every 21 days for three cycles with concurrent thoracic radiotherapy(TRT) (66 Gy/33 fractions), followed by consolidation chemotherapy with two cycles of pemetrexed(500mg/m2) + carboplatin (AUC，5) every 21 days.Maintenance pemetrexed(500mg/m2) will be administered after consolidation chemotherapy until disease progression or unacceptable toxicity . | Drug: Pemetrexed<br>* Pemetrexed(500mg/m2)every 21 days<br>* Other names: NSC-698037;Drug: Carboplatin<br>* Carboplatin (AUC，5) every 21 days<br>* Other names: Paraplatin;Radiation: Thoracic radiotherapy(TRT)<br>* TRT (total dose 66Gy, 2Gy per time, once a day, five times a week, a total of 33 times)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | A duration from randomization date to disease progression(as defined by RECIST) or death. If a participant are known to have progressed, the time to progression is defined as the time from the date of randomization to the date of progression. Otherwise, a participant will be censored at the last date they are known not to be progressed. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival(OS) | Overall survival is assessed via calculation of the time to death due to any cause. If a participant is known to have died, the time to death is defined as the time from the date of randomization to the date of death. Otherwise, a participant will be censored at the last date they are known to be alive. | two years | 
| Adverse events | The number of patients who suffered adverse events, which is graded by NCI CTCAE version 4.0. | two years | 
| Objective response rate | Number of subjects with confirmed objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. | two years | 
| Quality of life | Quality of life as measured by the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) questionnaire. | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR mutation, Inoperable stage III non-small cell lung cancer, Icotinib, Radiotherapy, Chemoradiotherapy