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

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ClinicalTrials.gov Identifier: NCT03544814
Recruitment Status : Completed
First Posted : June 4, 2018
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Tianqing Chu, Shanghai Chest Hospital

Tracking Information
First Submitted Date  ICMJE May 21, 2018
First Posted Date  ICMJE June 4, 2018
Last Update Posted Date October 15, 2019
Actual Study Start Date  ICMJE January 1, 2015
Actual Primary Completion Date June 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE EGFR-TKI Combined With Concurrent or Sequential Chemotherapy for Patients of Gradual Progression
Official Title  ICMJE 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
Brief Summary

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).

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lung Adenocarcinoma
  • EGFR Activating Mutation
Intervention  ICMJE
  • Drug: 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 Name: EGFR-TKI combined with chemotherapy
  • Drug: 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 Name: chemotherapy
Study Arms  ICMJE
  • Experimental: Concurrent therapy group
    Icotinib combined with pemetrexed plus cisplatin.
    Intervention: Drug: icotinib combined with pemetrexed plus cisplatin
  • Experimental: Sequential therapy group
    First icotinib and then pemetrexed plus cisplatin.
    Intervention: Drug: first icotinib and then pemetrexed plus cisplatin
Publications * Yang JJ, Chen HJ, Yan HH, Zhang XC, Zhou Q, Su J, Wang Z, Xu CR, Huang YS, Wang BC, Yang XN, Zhong WZ, Nie Q, Liao RQ, Jiang BY, Dong S, Wu YL. Clinical modes of EGFR tyrosine kinase inhibitor failure and subsequent management in advanced non-small cell lung cancer. Lung Cancer. 2013 Jan;79(1):33-9. doi: 10.1016/j.lungcan.2012.09.016. Epub 2012 Oct 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 11, 2019)
99
Original Actual Enrollment  ICMJE
 (submitted: May 31, 2018)
120
Actual Study Completion Date  ICMJE December 30, 2017
Actual Primary Completion Date June 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03544814
Other Study ID Numbers  ICMJE Chest006
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tianqing Chu, Shanghai Chest Hospital
Study Sponsor  ICMJE Shanghai Chest Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tianqing Chu Shanghai Chest Hospital
PRS Account Shanghai Chest Hospital
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP