Erlotinib Combined With Chemotherapy in TKI Resistant Non-Small Cell Lung Cancers

December 25, 2023 updated by: Yongchang Zhang, Hunan Province Tumor Hospital

Second Line Erlitinib Combination With Gemcitabine Cisplatinum in Non-small Cell Lung Cancer Patients Who Harbored EGFR Sensitive Mutation Developed Resistance After First Line TKI Treatment

Numerous evidences verified that erlotinib could dramatically improve the PFS and OS of non-small cell lung cancers who harbor EGFR sensitive mutations, however, primary or secondary resistance will be developed after TKI treatment, doctors do plenty of researches to overcome TKI resistance. FAST ACT-2 study present that, first line erlotinib combined with chemotherapy could improved mOS to more than 30 months in NSCLCs who harbor EGFR sensitive mutations, several study shows that sensitive mutations still exist after TKI resistance, because of the next generation TKIs(such as BIBW2992) are not avaliable at present, agents for met amplification(such as Crizotinib) are so expensive that many Chinese patients could not support. Thus, the investigators hypothesis that, after first line TKI treatment, the patients who developed TKI resistance could still benefit from second line TKI combined with chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators will enroll patients diagnosed with advanced non-squamous,non-small cell lung cancer, patients with EGFR TKI sensitive mutations and developed TKI resistance in first line treatment. After enrollment, the investigators will do biopsy again before second line treatment to find out the potential mechanism of TKI resistance, do EGFR mutation test for both sensitive and resistant mutation in exon 18, 19, 20 and 21; do KRAS, BRAF and PI3K mutation test, do FISH for MET and HER-2, the investigators do all these test to evaluated both primary and secondary resistance, the investigators do all these tests to get an overview for EGFR mutation status of each patient who develop TKI resistance. For second line treatment, patients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease. For the patients who have stable brain metastases, combined chemotherapy should begin after local treatment, such as whole brain radiotherapy or sterotactic radiosurgery.

the main endpoint of this study is mean PFS, second endpoints of this study consist of mean OS, 8 week ORR.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • China
    • Hunan
      • Changsha, Hunan, China
        • Recruiting
        • Hunan Province Tumor Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nong Yang, MD

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

Description

Inclusion Criteria:

  • advanced non-small cell lung cancer, stage IIIB/IV
  • non-squamous
  • EGFR sensitive mutations, such as exon 19 del, or exon 21 L858R
  • received first line TKIs treatment and developed TKI resistance
  • ECOG 0-2

Exclusion Criteria:

  • squamous non-small cell lung cancer
  • patients have unstable brain metastasis, predict survival less than 8 weeks
  • spinal-cord compression without evidence of stabilisation or treatment
  • women who were pregnant or lactating; women with a positive or no available pregnancy test result at baseline
  • patients have any unstable illness that could not receive further treatment

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: experimental
patients will received a 28 days gemcitabine platinum combined with erlotinib scheme(gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for 150mg/day, day 9-21 every cycle, after 4 cycles, erlotinib should be used daily), after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease.
Drug: Gemcitabine platinum combined with erlotinib
patients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycles combined chemotherapy, patients will receive erlotinib for maintain treatment until progression disease.Gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for day 9-21 during combined chemotherapy, 150mg/day, then erlotinib should be used daily until patients develop progression disease.
Other Names:
  • Gemzar
  • Tarceva

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mean progression free survival(mPFS)
Time Frame: after patients receive treatment, mPFS should be measured before the third cycle of chemotherapy, after the fourth cycle, mPFS should be measured every 3 months up to two years
mean progression free survival(mPFS) will be recorded in enroll patients who received second line gemcitabine platinum combined with erlotinib. mPFS should be measured before second line treatment, before the third combined chemotherapy, after the fourth combined chemotherapy, every 3 months during erlotinib treatment, mPFS should be measured up to two years or every time progression disease occurs within two years.
after patients receive treatment, mPFS should be measured before the third cycle of chemotherapy, after the fourth cycle, mPFS should be measured every 3 months up to two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mean overall survival(mOS)
Time Frame: every 3 months up to 3 years, or until all the survival data is obtained
mOS should be measured since enrollment, every 3 months we will contact patients to find out detail survival data of each patient until 3 years, or within 3 years if all survival data is obtained.
every 3 months up to 3 years, or until all the survival data is obtained
8 week overall response rate(8 week ORR)
Time Frame: 8 week ORR should be measured after enrollment, the exact time point should be the ninth week after combined chemotherapy
8 week ORR should be measured after enrollment, after combined chemotherapy for 8 weeks, the exact time point should be the ninth week during combined chemotherapy. CR, PR, SD shoud be measured according to RESICT 1.1
8 week ORR should be measured after enrollment, the exact time point should be the ninth week after combined chemotherapy

Collaborators and Investigators

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

Sponsor

Hunan Province Tumor Hospital

Investigators

  • Study Chair: Nong Yang, MD, Hunan Province Tumor Hospital

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)

July 1, 2014

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 12, 2025

Study Registration Dates

First Submitted

March 20, 2014

First Submitted That Met QC Criteria

March 25, 2014

First Posted (Estimated)

March 28, 2014

Study Record Updates

Last Update Posted (Estimated)

December 27, 2023

Last Update Submitted That Met QC Criteria

December 25, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TKIRR001

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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