Gefitinib Versus Vinorelbine/Platinum as Adjuvant Treatment in Stage II-IIIA(N1-N2) NSCLC With EGFR Mutation

Non-small Cell Lung Cancer Clinical Trial

— ADJUVANT  

Official title:

A Randomized, Open-label Trial of Gefitinib Versus Combination of Vinorelbine Plus Platinum as Adjuvant Treatment in Pathological Stage II-IIIA(N1-N2) Non-small Cell Lung Cancer With EGFR Mutation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01405079
• Other study ID #: CTONG 1104
• Secondary ID: CTONG 1104
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 19, 2011
• Est. completion date: December 2020

Study information

• Verified date: February 2020
• Source: Guangdong Association of Clinical Trials
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese Non-small Cell Lung Cancer(NSCLC). Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.

Description:

Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA non-small cell lung cancer (NSCLC) after complete resection. Cisplatin and vinorelbine combination is the standard of care in adjuvant setting. The BR. 19 trial reported adjuvant gefitinib after complete resection of early stage NSCLC(stage IB 49%, II 38%, III 13%) did not confer disease free survival(DFS) or overall survival(OS) advantage in overall population. While the median gefitinib treatment time is only 4.8 months. There are only 76 patients with EGFR mutations included in this analysis. The study closed prematurely in 2005.

Activating somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor (EGFR) have been characterized in a subset of patients with advanced NSCLC.The EGFR mutation rate was 30% in Chinese NSCLC. Patients harboring these mutations in their tumors show excellent response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). This randomized phase III trial is studying gefitinib to see how well it works compared to cisplatin-based chemotherapy in treating patients who have undergone surgery for stage II-IIIA(N1-N2) NSCLC with EGFR activating mutation in Asian population.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 222
• Est. completion date: December 2020
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Written informed consent provided.

• Males or females aged =18 years, < 75 years.

• Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.

• Target population is completely resected pathological stage II-IIIA(N1-N2) NSCLC with EGFR exon 19 deletions and exon 21 L858R activating mutation.

• Patient who can start the investigational therapy within 3-6 weeks after the complete resection

• ECOG performance status 0-1.

• Life expectancy =12 weeks.

• Adequate hematological function: Absolute neutrophil count (ANC) =2.0 x 109/L, and Platelet count =100 x 109/L, and Hemoglobin =9 g/dL (may be transfused to maintain or exceed this level).

• Adequate liver function: Total bilirubin = 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) = 2.5 x ULN in subjects without liver metastases; = 5 x ULN in subjects with liver metastases.

• Adequate renal function: Serum creatinine = 1.25 x ULN, or = 60 ml/min.

• Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria:

• Known severe hypersensitivity to gefitinib or any of the excipients of this product.

• Known severe hypersensitivity to pre-medications required for treatment with cisplatin / vinorelbine doublet chemotherapy.

• Inability to comply with protocol or study procedures.

• A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.

• A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.

• Interstitial pneumonia.

• Patients with prior exposure to agents directed at the HER axis (e.g. erlotinib, gefitinib, cetuximab, trastuzumab).

• Patients with prior chemotherapy or therapy with systemic anti-tumour therapy (e.g. monoclonal antibody therapy).

• Patients with prior radiotherapy

• History of another malignancy in the last 5 years with the exception of the following:Other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.

• Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).

• Eye inflammation or eye infection not fully treated or conditions predisposing the subject to this.

• Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.

• Patient who has active serious infection (e.g. pyrexia of or 38.0? over)

• Patients who harbouring exon 20 T790M mutation.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Gefitinib
Gefitinib 250 mg/day oral daily
• Vinorelbine+Cisplatin
Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles

Locations

Country	Name	City	State
China	Guangdong General Hospital	Guangzhou

Sponsors (26)

Lead Sponsor

Collaborator

Guangdong Association of Clinical Trials

309th Hospital of Chinese People's Liberation Army, Beijing Cancer Hospital, Beijing Chest Hospital, Chinese PLA General Hospital, First Affiliated Hospital, Sun Yat-Sen University, First Hospital of China Medical University, Fudan University, Guangdong Provincial People's Hospital, Jiangsu Cancer Institute & Hospital, Jilin Provincial Tumor Hospital, Liaoning Tumor Hospital & Institute, Peking Union Medical College Hospital, Peking University First Hospital, Peking University People's Hospital, Shanghai Pulmonary Hospital, Shanghai, China, Sun Yat-sen University, Tang-Du Hospital, The Affiliated Hospital of Qingdao University, The First Affiliated Hospital of Soochow University, Tianjin Medical University Cancer Institute and Hospital, Tongji Hospital, West China Hospital, Wuhan Union Hospital, China, Zhejiang Cancer Hospital, Zhejiang University

Country where clinical trial is conducted

China, 

References & Publications (1)

Janjigian YY, Park BJ, Zakowski MF, Ladanyi M, Pao W, D'Angelo SP, Kris MG, Shen R, Zheng J, Azzoli CG. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations. J Thorac Oncol. 2011 Mar;6(3):569-75. doi: 10.1097/JTO.0b013e318202bffe. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival	To evaluate the disease free survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for pathological stage II-IIIA(N1-N2) NSCLC with EGFR mutation.Disease free survival (DFS)- defined as the time from randomization to the first documented disease progression or death, whichever occurs first.	Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone.
Secondary	Overall survival	To evaluate the overall survival of gefitinib versus combination of vinorelbine plus platinum as adjuvant treatment for stage II-IIIA(N1-N2) NSCLC with EGFR mutation.	Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone.
Secondary	3 yeas DFS rate, 5 years DFS rate, 5 years OS rate	To compare the randomized treatment arms in terms of 3 yeas DFS rate, 5 years DFS rate, 5 years OS rate.	Pts after surgery will receive long-term follow-up including chest CT scan, abdominal ultrasound every 3 months, brain MRI every 6 months, bone scan every 12 months for up to 3 years. The survival after 3 years will be followed up with telephone.
Secondary	Number of Participants with Adverse Events	The safety and tolerability profile of gefitinib at a 250 mg daily dose relative to that of Chemotherapy.	In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles.
Secondary	The Total Score and TOI of FACT-L to Measure Quality of life	Quality of life as measured by the total score and Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) questionnaire.	In the period of Gefitinib 250 mg/day oral daily for 24 months.Vinorelbine 25 mg/m2 intravenous infusion on day 1 and day 8, Cisplatin 75 mg/m2 on day 1 for 4 cycles.