Clinical Trial of Neoadjuvant Targeted Treatment to NSCLC Patients

Oral Navelbine Carboplatin Versus Gefitinib Neoadjuvant Therapy for Resectable EGFR Mutation Positive Stage Ⅱ-ⅢA NSCLC, Prospective, Randomized, Multicenter, Phase Ⅲ Clinical Trial

The purpose of this study is to evaluate the efficiency and safety of Gefitinib Neoadjuvant Therapy and Oral Navelbine Carboplatin Neoadjuvant Therapy for Resectable Stage Ⅱ-ⅢA NSCLC patients with EGFR mutation.

Study Overview

• Status: Not yet recruiting
• Conditions: 2-year Disease-Free Survival
• Intervention / Treatment: Drug: Oral Navelbine + Carboplatin; Drug: Gefitinib

Detailed Description

Lung cancer is the most common cause of cancer mortality in men and women in the world. LACE meta analysis shows that the 5-year survival rate of post-operation chemotherapy group rose by 5.4%, therefore, adjuvant chemotherapy has been the main treatment after surgery according to National Comprehensive Cancer Network (NCCN) Guideline. But patients have poor compliance due to physical condition after surgery. Compared with adjuvant chemotherapy, neoadjuvant therapy has better patient compliance and tolerance.Targeted therapy, with milder side effect compared with chemotherapy, may be a promising choice to treat NSCLC previously. But to date, there is no enough evidence to support the efficacy and safety of neoadjuvant targeted therapy in patients with EGFR mutation.The purpose of this study is to evaluate the efficiency and safety of Gefitinib Neoadjuvant Therapy vs Oral Navelbine Carboplatin Neoadjuvant Therapy for Resectable NSCLC patients harboring EGFR mutation.

• Study Type: Interventional
• Enrollment (Anticipated): 590
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Guowei Ma, MD; Phone Number: 13501546669; Email: magw@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Dongguan, Guangdong, China, 523000
      • Dongguan people's hospital
      • Contact: Jianping Zhou, MD
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen University Cancer Center
      • Contact: Guowei Ma, MD; Email: magw@sysucc.org.cn
      • Principal Investigator: Guowei Ma
    • Guangzhou, Guangdong, China, 510000
      • The Sixth Affiliated Hospital of Sun Yat-sen University
      • Contact: Jinming Zhao, MD
    • Maoming, Guangdong, China, 525000
      • Maoming Affiliated Hospital of Southern Medical University
      • Contact: Jiang Huang, MD
    • Shenzhen, Guangdong, China, 518000
      • ShenZhen People's Hospital
      • Contact: Guangsuo Wang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologic diagnosis of non small cell lung cancer, Stage Ⅱ-ⅢA before treatment
• EGFR Gene mutated
• ECOG 0-1
• liver, kidney and bone marrow are functional healthy，WBC>4.0×109/L，PLT>100×109/L Hb>10g/dL;Cr<1.8mg/dL，bilirubin<1.5mg/dL，GPT<1.5 upper limit of normal
• No vital systems dysfunction or malnutrition
• No other malignant diseases in 5 years（except non melanoma or Cervical carcinoma in situ）
• Have never accepted radiation therapy、overall chemotherapy or biotherapy
• Know the whole protocol，Voluntary participate and sign a consent form

Exclusion Criteria:

• Tumor has violated the surrounding tissue organs（T4）
• Preoperative have evidence of distant metastasis including the contralateral mediastinal lymph nodes
• Arrhythmia need anti-arrhythmic treatment（except for β-blockers or digoxin），Symptomatic coronary artery disease and myocardial ischemia (myocardial infarction) in the past 6 months or more than NYHA class II congestive heart failure
• Adverse drug control severe hypertension
• Moderate to severe proteinuria
• History of HIV infection or activity of chronic hepatitis b or hepatitis c, or other active clinical severe infection
• Cachexy,organ function decompensation
• History of chest radiotherapy
• Not fully control the eye inflammation
• Epilepsy patients needed treatment（such as Steroids or antiepileptic cure）
• Interstitial pneumonia
• Drug abuse and medical, psychological or social conditions may interfere with the patients involved in the research or have an impact on the results of evaluation
• Known or suspected to study drug allergy or to give any drug allergies associated with this test
• Any unstable situation or may endanger the patient safety and compliance
• Fertility and pregnancy or lactation women, and have not been sufficient precautions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Navelbine + Carboplatin; Neoadjuvant therapy Patients with EGFR mutation will be recruited and treated with Navelbine + Carboplatin.	Drug: Oral Navelbine + Carboplatin; The patient will be given Navelbine 60 mg/m2, p.o. day 1 and 8 of every cycle (21 days) plus carboplatin AUC 5, i.v. day 1 of every cycle.After 2 cycle we will evaluate their clinical response.Then operable patients will have surgery.; Other Names: Carboplat; Vinorelbine
Experimental: Gefitinib; Neoadjuvant therapy Patients with EGFR mutation will be recruited and treated with gefitinib.	Drug: Gefitinib; The patient will be given Gefitinib 250mg,p.o.,q.d. for 8 weeks.After 8 weeks we evaluate their clinical response.Then operable patients will have surgery.; Other Names: Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year disease free survival	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	1 week before surgery
Pathologic complete response	Within 1 month after surgery
Side effects	1 week before surgery
Standard uptake value	1 week before surgery
Tumor reduction rate	Within 1 month after surgery
Mediastinal lymph nodes clearance	Within 1 month after surgery
Postoperative complications	Within 1 month after discharge
R0 resection rate	Within 1 month after surgery
Postoperative mortality rate	Within 1 month after discharge
5-year overall survival	5 years after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Shenzhen People's Hospital; Sixth Affiliated Hospital, Sun Yat-sen University; Dongguan People's Hospital; Maoming Affiliated Hospital of Southern Medical University
• Investigators: Principal Investigator: Guowei Ma, MD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): January 1, 2026
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (Actual): June 29, 2017

Study Record Updates

• Last Update Posted (Actual): June 29, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Gefitinib; Vinorelbine
• Other Study ID Numbers: 3939366

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No