EGFR-TKI Combined With Concurrent or Sequential Chemotherapy for Patients of Gradual Progression

October 11, 2019 updated by: Tianqing Chu, Shanghai Chest Hospital

EGFR Tyrosine Kinase Inhibitor Combined With Concurrent or Sequential Chemotherapy for Advanced Lung Cancer Patients of Gradual Progression After First-line EGFR-TKI Therapy: a Randomized Controlled Study

To compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential treatment after patients gradually progressed from first-line EGFR-TKI treatment.

Patients who had gradual progression and EGFR-T790M mutation-negative were randomly divided into two groups: in concurrent group, patients were treated with pemetrexed plus cisplatin along with the same EGFR-TKI; in sequential group, patients continued with EGFR-TKI until the disease progressed again according to the RECIST criteria, and then switched to chemotherapy. We evaluated progression-free survival (PFS) and overall survival (OS) time of patients. For sequential group, PFS was PFS1 (gradual progression to discontinue EGFR-TKI) plus PFS2 (chemotherapy alone).

Study Overview

Detailed Description

According to previous reports, when non-small cell lung cancer (NSCLC) patients with EGFR mutations gradually progressed after initial EGFR tyrosine-kinase inhibitor (TKI) treatment, continuing TKI therapy may be beneficial. We aimed to compare the efficacy of simultaneous EGFR-TKI and chemotherapy with that of sequential treatment after patients gradually progressed from first-line EGFR-TKI treatment.

Patients who had gradual progression and EGFR-T790M mutation-negative were randomly divided into two groups: in concurrent group, patients were treated with pemetrexed plus cisplatin along with the same EGFR-TKI; in sequential group, patients continued with EGFR-TKI until the disease progressed again according to the RECIST criteria, and then switched to chemotherapy. We evaluated progression-free survival (PFS) and overall survival (OS) time of patients. For sequential group, PFS was PFS1 (gradual progression to discontinue EGFR-TKI) plus PFS2 (chemotherapy alone). Objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety were also evaluated.

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 2

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 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Patients had to voluntarily join the study and give written informed consent for the study
  2. Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV adenocarcinoma.
  3. A cytologic diagnosis is acceptable (i.e., FNA or pleural fluid cytology)
  4. Sensitive EGFR mutations (exon 19 deletion or L858R mutation in exon 21)
  5. At least one measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST) criteria.
  6. Patients achieved the gradual progression after first-line EGFR-TKI therapy.

The criteria of gradual progression:

  1. disease control≥6 months with EGFR-TKI treatment;
  2. compared with the previous assessment,no significant increment of tumor burden and progressive involvement of non-target lesions with a score ≤2;
  3. symptom scored≤1. 7) Patients did not achieve acquired EGFR-T790M mutation assessed by ARMS, next-generation sequencing (NGS) or droplet digital PCR (ddPCR) after first-line EGFR-TKI therapy 8) Patients did not receive any chemotherapy previously 9) Able to comply with study and follow-up procedures 10) Age >=18 years, ECOG PS: 0~2, estimated survival duration more than 3 months; 11) Major organ function

Exclusion criteria:

  1. Other types of non-small cell lung cancer except adenocarcinoma and Small cell lung cancer(including patients with mixed small cell lung cancer and non-small cell lung cancer);
  2. Evidence of other types of non-small cell lung cancer except adenocarcinoma, small cell, carcinoid, or mixed small cell/non-small cell histology
  3. EGFR wild-type patients, or patients with rare EGFR mutations or complex EGFR mutations
  4. Patients achieved the dramatic progression after first-line EGFR-TKI therapy. The criteria of dramatic progression
  5. Patients achieved the local progression after first-line EGFR-TKI therapy. The criteria of local progression
  6. Patients achieved acquired EGFR-T790M mutation assessed by ARMS, next-generation sequencing (NGS) or droplet digital PCR (ddPCR) after first-line EGFR-TKI therapy
  7. Previously (within 5 years) or presently suffering from other malignancies
  8. A in situ,non-melanoma skin cancers and superficial bladder cancer
  9. Unstable systemic disease
  10. 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
  11. Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, or prior surgical procedures affecting absorption
  12. Pregnancy or lactation

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: Concurrent therapy group
Icotinib combined with pemetrexed plus cisplatin.
Continued using the icotinib (125 mg/time, 3 times/day every day) combined with Pemetrexed (500 mg/㎡ on day 1) plus cisplatin (75mg/m2 on day 1) and repeat every four weeks for up to six cycles and then continue to receive pemetrexed combined with icotinib every four weeks.
Other Names:
  • EGFR-TKI combined with chemotherapy
Experimental: Sequential therapy group
First icotinib and then pemetrexed plus cisplatin.
Continued using the icotinib (125 mg/time, 3 times/day every day)) alone until the investigator judged that continuation was adiaphorous, and switched to Pemetrexed (500 mg/㎡ on day 1) plus cisplatin (75mg/m2 on day 1) alone, repeat every four weeks for up to six cycles and then continue to receive pemetrexed every four weeks.
Other Names:
  • chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 16 months
Radiographic assessments were performed when enrolled and every 8 weeks until disease progression after chemotherapy according to RECIST version 1.1. After PD, collect the survival information every 16 weeks until death or withdrawal of study consent.
16 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival (OS)
Time Frame: 32 months
Radiographic assessments were performed when enrolled and every 8 weeks until disease progression after chemotherapy according to RECIST version 1.1. After PD, collect the survival information every 16 weeks until death or withdrawal of study consent.
32 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Tianqing Chu, Shanghai chest hospital

Publications and helpful links

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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)

January 1, 2015

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

December 30, 2017

Study Registration Dates

First Submitted

May 21, 2018

First Submitted That Met QC Criteria

May 31, 2018

First Posted (Actual)

June 4, 2018

Study Record Updates

Last Update Posted (Actual)

October 15, 2019

Last Update Submitted That Met QC Criteria

October 11, 2019

Last Verified

January 1, 2015

More Information

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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