Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced EGFR-mutant NSCLC

November 23, 2017 updated by: You Lu, Sichuan University

A Randomized, Open-label, Multiple-centre Study of Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced NSCLC With EGFR Mutation Positive

Study Title:

Intercalating and maintenance Gefitinib in combination with chemotherapy (gemcitabine plus carboplatin) as first-line treatment for patients with advanced EGFR mutation-positive non-small cell lung cancer: A randomized, open-label, multiple-centre study.

Target population-Treatment naive EGFR mutant-positive advanced NSCLC patients.

Study Objectives - Primary Study Objective: To investigate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Progression-Free Survival (PFS) vs. Gefitinib alone in advanced NSCLC with EGFR activating mutation.

- Secondary Study Objective： To evaluate whether intercalating and maintenance Gefitinib in combination with chemotherapy improve the Objective Response Rate (ORR), Disease control rate (DCR), Overall survival (OS), 2-year OS rate, QOL vs. Gefitinib alone.

Evaluation the safety of Intercalating and Maintenance Gefitinib in combination with chemotherapy.

- Exploratory objective: PFS of arm A vs. PFS 1 + PFS 2 of arm B Dynamic biomarker analysis using blood sample

a: The PFS 1 of arm B is the time from randomization to disease progression of 1st-line therapy or death from any cause, whichever occurs first. The PFS 2 of arm B is the time from the time of PFS 1 to disease progression of 2nd-line therapy or death from any cause, whichever occurs first.

Study Design-Prospective, open-label, randomized, multi-center study.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Study Design:

It is a two-arm, prospective, randomized, open-label, multi-center study. The study will be conducted at 5 study sites in China. West China Hospital serves as the lead site for the study. A total of 146 treatments naive EGFR mutant positive advanced NSCLC patients are planned to be enrolled into this study.

There are four periods in this study: baseline period (≤28days),main phase of treatment (Week 0-Week 16 or until disease progression),post-treatment period and follow-up until about 24 months after the last patients enrolment.

  1. Baseline period: Subject will be enrolled in the study after signing informed consent form (ICF). Investigator will record patient-reported outcome, demographic data and medical history, collect the histological or cytological samples for genetic testing, conduct laboratory examination and perform imaging examination and so on. Notes: The time of imagination is effective within 4 weeks before treatment. The result of haematology, biochemistry and physical examination is effective within 7 days before treatment. Collecting blood one time at screening period (The SOP of blood collection, storage and transportation is in attachment 1).

  2. Main phase of treatment: There are 8 visits during the main phase of treatment study. During the main phase of treatment, investigator conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety.

    Collecting blood one time every two cycles (The SOP of blood collection, storage and transportation is in attachment 1).

  3. Post-treatment period:

    In the study group, investigators will conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety until disease progression every 8 weeks. And after disease progression investigators will enquire and record survival status of subjects every 8 weeks.

    In the control group, investigators will conduct laboratory examination, perform imaging examination, assess the tumor status, and evaluate the patient-reported outcome and safety until the first and the second disease progression every 8 weeks. In addition, the information conduct between first disease progression and second progression are optional, but should be collected if available. And after the second disease progression investigators will enquire and record survival status of subjects every 8 weeks.

    Collecting blood one time every 8 weeks until progress (for control group it will be until the first progress)

  4. Follow-up period:

It will last until about 24 months after the last patients' enrolment. Accesses histological or cytological samples for EGFR testing and related drug resistant gene testing are required. In addition, collection blood is optional, but should be collected if available. All the samples collected during his/her whole life treatment are transported to West China Hospital to store and will be used for further exploratory analysis later.

All results of CT/MRI need to be burned into compact disc (CD). This study will be the first study to compare the efficacy of intercalating and maintenance gefitinib in combination with chemotherapy to gefitinib alone as first-line treatment for patients with advanced EGFR activating mutation-positive non-small cell lung cancer.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Sichuan
      • Chengdu, Sichuan, China, 610000
        • China West Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects enrolled in this study are required to meet the following inclusion criteria:

    1. Patients between 18 and 75 years of age.
    2. Patients with histologically or cytologically diagnosed NSCLC,or patients with recurrent advanced NSCLC after surgery.
    3. Harboring activating mutation of EGFR,only including an exon 19 deletion or an exon 21 point mutation.
    4. Has at least one measureable lesion by RECIST 1.1
    5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
    6. No prior systemic chemotherapy or targeted therapy for lung cancer before screening except neoadjuvant or adjuvant patients.

    7. Adequate organ function, including the following:

      Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 × 109/L,platelets ≥100 × 109/L,and hemoglobin ≥9 g/dL.

      Hepatic: bilirubin ≤1.5 times the upper limit of normal (× ULN),alkaline phosphatase (AP),aspartate transaminase (AST),and alanine transaminase (ALT) ≤3.0 × ULN (AP,AST and ALT ≤5 × ULN is acceptable if the liver has tumor involvement).

      Renal: calculated creatinine clearance (CrCl) ≥45 mL/minute based on the standard Cockcroft and Gault formula.

    8. Prior radiation therapy allowed to <25% of the bone marrow. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study enrolment.
    9. Signed informed consent document on file.
    10. Estimated life expectancy of ≥12 weeks.

    11. Patient compliance and geographic proximity that allow adequate follow up.

      Exclusion Criteria:

  • Subjects meeting any of the following exclusion criteria are not to be enrolled in the study.

    1. Known severe hypersensitivity to gefitinib.
    2. Known brain metastasis unless asymptomatic brain metastasis(without neurotic symptoms and sign) and treated with surgery and/or radiation and stable without steroid treatment for at least 2 weeks prior to the first dose of study medication.
    3. Pleural effusion or pericardiac effusion that cannot be controlled by drainage or other procedures.
    4. Previous treatment with agents targeting the HER axis.
    5. Previous systemic antitumour treatment.
    6. The last regimen of neoadjuvant or adjuvant treatment for non-metastatic disease within 12 months of study treatment.
    7. EGFR Resistance mutation (+).
    8. Surgery undertaken less than 4 weeks before the study.
    9. Inability to comply with protocol or study procedures.
    10. A serious concomitant systemic disorder that,in the opinion of the investigator，would compromise the patient's ability to complete the study.
    11. A serious cardiac condition,such as myocardial infarction within 6 months,angina,or heart disease.
    12. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
    13. Past medical history of Interstitial Lung Disease(ILD),drug induced interstitial disease,radiation pneumonitis which required steroid treatment,or any evidence of clinically active ILD.
    14. Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline.
    15. Unwillingness to use contraception during the study, women who were pregnant or lactating.
    16. Being or planing to participate in other studies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A

Four cycles gemcitabine(d1,8 ) + carboplatin (d1) + gefitinib (15-25), gefitinib 250mg/d from d15 of last cycle until disease progression.

Gemcitabine=1000mg/m2;Carboplatin 5×AUC ; One cycle is 28 days
Drug: Gefitinib
patients in arm A will be given gefitinib as target therapy
Other Names:
  • Iressa
Drug: gemcitabine
patients in arm A will be given gemcitabine chemotherapy
Other Names:
  • Gemza
Drug: carboplatin
patients in arm A will be given carboplatin chemotherapy
Other Names:
  • Carboplatin Injection
Active Comparator: Arm B
Gefitinib 250mg/d until disease progression
Drug: Gefitinib
patients in arm A will be given gefitinib as target therapy
Other Names:
  • Iressa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression free survival - PFS
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective Response Rate - ORR
Time Frame: at day 42 of treatment
at day 42 of treatment
Overall Survival - OS
Time Frame: the time from randomization to death from any cause,assessed up to 2 years
the time from randomization to death from any cause,assessed up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sichuan University

Collaborators

AstraZeneca

Investigators

  • Study Director: You Lu, MD, Department of Thoracic Oncology, Cancer center, West China Hospital, Sichuan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2014

Primary Completion (Actual)

October 1, 2017

Study Completion (Actual)

October 1, 2017

Study Registration Dates

First Submitted

November 18, 2014

First Submitted That Met QC Criteria

November 20, 2014

First Posted (Estimate)

November 24, 2014

Study Record Updates

Last Update Posted (Actual)

November 27, 2017

Last Update Submitted That Met QC Criteria

November 23, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ISSIRES0109

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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