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

NCT03544814 | Completed Phase 2

• 1 other identifier: Chest006
• Study Type: interventional
• Target: 99
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Lung Adenocarcinoma; EGFR Activating Mutation

Outcome Measures

Primary Outcomes (1)

• 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.

  16 months

Secondary Outcomes (1)

• overall survival (OS)

  32 months

Study Arms (2)

Concurrent therapy group

EXPERIMENTAL

Icotinib combined with pemetrexed plus cisplatin.

Drug: icotinib combined with pemetrexed plus cisplatin

Sequential therapy group

EXPERIMENTAL

First icotinib and then pemetrexed plus cisplatin.

Drug: first icotinib and then pemetrexed plus cisplatin

Interventions

icotinib combined with pemetrexed plus cisplatin 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.

Also known as: EGFR-TKI combined with chemotherapy

Concurrent therapy group

first icotinib and then pemetrexed plus cisplatin 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.

Also known as: chemotherapy

Sequential therapy group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Chest Hospital: lead

Related Publications (1)

• 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.

  PMID: 23079155 BACKGROUND

MeSH Terms

Conditions

Adenocarcinoma of Lung

Interventions

Pemetrexed; Cisplatin; Drug Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Tianqing Chu

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: May 21, 2018
• First Posted: June 4, 2018
• Study Start: January 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: December 30, 2017
• Last Updated: October 15, 2019

Record last verified: 2015-01

Data Sharing

• IPD Sharing: Will not share