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

Primary Purpose

Lung Adenocarcinoma, EGFR Activating Mutation

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

icotinib combined with pemetrexed plus cisplatin

first icotinib and then pemetrexed plus cisplatin

About this trial

This is an interventional treatment trial for Lung Adenocarcinoma

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria：

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

The criteria of gradual progression:

disease control≥6 months with EGFR-TKI treatment;
compared with the previous assessment，no significant increment of tumor burden and progressive involvement of non-target lesions with a score ≤2;
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：

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）；
Evidence of other types of non-small cell lung cancer except adenocarcinoma, small cell, carcinoid, or mixed small cell/non-small cell histology
EGFR wild-type patients, or patients with rare EGFR mutations or complex EGFR mutations
Patients achieved the dramatic progression after first-line EGFR-TKI therapy. The criteria of dramatic progression
Patients achieved the local progression after first-line EGFR-TKI therapy. The criteria of local progression
Patients achieved acquired EGFR-T790M mutation assessed by ARMS, next-generation sequencing (NGS) or droplet digital PCR (ddPCR) after first-line EGFR-TKI therapy
Previously (within 5 years) or presently suffering from other malignancies
A in situ，non-melanoma skin cancers and superficial bladder cancer
Unstable systemic disease
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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Concurrent therapy group

Sequential therapy group

Arm Description

Icotinib combined with pemetrexed plus cisplatin.

First icotinib and then pemetrexed plus cisplatin.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)

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.

Secondary Outcome Measures

overall survival (OS)

Full Information

NCT ID

NCT03544814

First Posted

May 21, 2018

Last Updated

October 11, 2019

Sponsor

Shanghai Chest Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03544814

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

January 1, 2015 (Actual)

Primary Completion Date

June 1, 2017 (Actual)

Study Completion Date

December 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai Chest Hospital

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Adenocarcinoma, EGFR Activating Mutation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Concurrent therapy group

Arm Type

Experimental

Arm Description

Icotinib combined with pemetrexed plus cisplatin.

Arm Title

Sequential therapy group

Arm Type

Experimental

Arm Description

First icotinib and then pemetrexed plus cisplatin.

Intervention Type

Drug

Intervention Name(s)

icotinib combined with pemetrexed plus cisplatin

Other Intervention Name(s)

EGFR-TKI combined with chemotherapy

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

first icotinib and then pemetrexed plus cisplatin

Other Intervention Name(s)

chemotherapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

Time Frame

16 months

Secondary Outcome Measure Information:

Title

overall survival (OS)

Description

Time Frame

32 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria： Patients had to voluntarily join the study and give written informed consent for the study Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV adenocarcinoma. A cytologic diagnosis is acceptable (i.e., FNA or pleural fluid cytology) Sensitive EGFR mutations (exon 19 deletion or L858R mutation in exon 21) At least one measurable lesion meeting Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Patients achieved the gradual progression after first-line EGFR-TKI therapy. The criteria of gradual progression: disease control≥6 months with EGFR-TKI treatment; compared with the previous assessment，no significant increment of tumor burden and progressive involvement of non-target lesions with a score ≤2; 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： 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）； Evidence of other types of non-small cell lung cancer except adenocarcinoma, small cell, carcinoid, or mixed small cell/non-small cell histology EGFR wild-type patients, or patients with rare EGFR mutations or complex EGFR mutations Patients achieved the dramatic progression after first-line EGFR-TKI therapy. The criteria of dramatic progression Patients achieved the local progression after first-line EGFR-TKI therapy. The criteria of local progression Patients achieved acquired EGFR-T790M mutation assessed by ARMS, next-generation sequencing (NGS) or droplet digital PCR (ddPCR) after first-line EGFR-TKI therapy Previously (within 5 years) or presently suffering from other malignancies A in situ，non-melanoma skin cancers and superficial bladder cancer Unstable systemic disease 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tianqing Chu

Organizational Affiliation

Shanghai Chest Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23079155

Citation

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.

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

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