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

NCT ID: NCT03544814

Last Updated: 2019-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-01
• Study Completion Date: 2017-12-30

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.

Conditions

Lung Adenocarcinoma; EGFR Activating Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Concurrent therapy group

Icotinib combined with pemetrexed plus cisplatin.

Group Type: EXPERIMENTAL

icotinib combined with pemetrexed plus cisplatin

Intervention Type: DRUG

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.

Sequential therapy group

First icotinib and then pemetrexed plus cisplatin.

Group Type: EXPERIMENTAL

first icotinib and then pemetrexed plus cisplatin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

EGFR-TKI combined with chemotherapy; chemotherapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Chest Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tianqing Chu

Associate Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tianqing Chu

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital

References

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.

Reference Type: BACKGROUND

PMID: 23079155 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol

View Document

Other Identifiers

Chest006

Identifier Type: -

Identifier Source: org_study_id