Combination of Chemotherapy and Gefitinib as First-line Treatment

Combination of Chemotherapy and Gefitinib as First-line Treatment of Patients With Advanced Lung Adenocarcinoma and Sensitive EGFR Mutations: a Randomised Controlled Trial

The results of fastact2 show that chemotherapy plus erlotinib significantly prolonged PFS and OS of patients with NSCLC. However, outcome of the combination therapy are similar to those reported in several trials of single-agent EGFR TKIs. So which is the optimal first-line treatment for patients who harbored a sensitive EGFR mutation? The investigators need a head-to-head study to reply.

Study Overview

• Status: Completed
• Conditions: Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: gefitinib; Drug: pemetrexed plus carboplatin

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200030
    • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent
2. Age >=18 years
3. Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic Stage IV Non-Small Cell Lung Cancer (NSCLC)
4. A cytologic diagnosis is acceptable (i.e., FNA or pleural fluid cytology)
5. Measurable or non-measurable disease
6. Able to comply with study and follow-up procedures

Exclusion Criteria:

• Evidence of small cell, carcinoid, or mixed small cell/non-small cell histology
• Malignancies within 3 years except for adequately treated carcinoma in situ of -the cervix or basal or squamous cell skin cancer
• Symptomatic or untreated brain metastases
• Prior systemic chemotherapy for NSCLC
• Unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or serious cardiac arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia, are eligible)
• History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications
• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, or prior surgical procedures affecting absorption
• Pregnancy or lactation

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chemotherapy group(B); pemetrexed plus carboplatin pemetrexed (500 mg/m(2) on day 1) plus carboplatin (AUC 5 on day 1) every 4 weeks for up to six cycles, then continued to receive pemetrexed(500 mg/m(2) on day 1) alone every 4 weeks	Drug: pemetrexed plus carboplatin; Other Names: Alimita plus carboplatin
Experimental: combination therapy group(A); pemetrexed (500 mg/m(2) on day 1) plus carboplatin (AUC 5 on day 1) combined with gefitinib (250 mg/day on days 5-21) and repeated every 4 weeks for up to six cycles,then continued to receive pemetrexed combined with gefitinib every 4 weeks.	Drug: gefitinib; Other Names: Iressa; Drug: pemetrexed plus carboplatin; Other Names: Alimita plus carboplatin
Experimental: gefitinib group (group C); received gefitinib( 250 mg/day)alone. All therapies of 3 groups were continued until progression or unacceptable toxicity or death	Drug: gefitinib; Other Names: Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression-free survival	6-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		2 years
to evaluate the safety profile between three groups	Toxicity will be graded according to NCI CTCAE, version 4.0. The analysis of safety/tolerability data will be descriptive; toxicity events will be individually tabulated.	6 months

Collaborators and Investigators

• Sponsor: Baohui Han
• Investigators: Study Chair: Baohui Han, Dr, Vice President of Shanghai Chest Hospital,Sponsor of study; Study Director: Bo Jin, Dr, Study Leader,Doctor of Shanghai Chest Hospital; Principal Investigator: Yanjie Niu, Master, Doctor of Shanghai Chest Hospital; Principal Investigator: Yanwei Zhang, Dr, Doctor of Shanghai Chest Hospital; Principal Investigator: Tianqing Chu, Dr, Doctor of Shanghai Chest Hospital; Principal Investigator: Aiqin Gu, Master, Doctor of Shanghai Chest Hospital; Principal Investigator: Lei Zhu, Master, Doctor of Shanghai Chest Hospital; Principal Investigator: Jun Pei, Doctor of Shanghai Chest Hospital

Publications and helpful links

General Publications

• Lou Y, Xu J, Zhang Y, Lu J, Chu T, Zhang X, Wang H, Zhong H, Zhang W, Han B. Chemotherapy Plus EGFR-TKI as First-Line Treatment Provides Better Survival for Advanced EGFR-Positive Lung Adenocarcinoma Patients: Updated Data and Exploratory In Vitro Study. Target Oncol. 2020 Apr;15(2):175-184. doi: 10.1007/s11523-020-00708-y.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: May 21, 2014
• First Submitted That Met QC Criteria: May 27, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: April 19, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Lung adenocarcinoma,EGFR mutation, chemotherapy, gefitinib
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; Carboplatin; Gefitinib; Pemetrexed
• Other Study ID Numbers: chest20140001

Plan for Individual participant data (IPD)

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