Erlotinib Combined With Chemotherapy in TKI Resistant Non-Small Cell Lung Cancers

NCT02098954 | Unknown Phase 2

• 1 other identifier: TKIRR001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Numerous evidences verified that erlotinib could dramatically improve the PFS and OS of non-small cell lung cancers who harbor EGFR sensitive mutations, however, primary or secondary resistance will be developed after TKI treatment, doctors do plenty of researches to overcome TKI resistance. FAST ACT-2 study present that, first line erlotinib combined with chemotherapy could improved mOS to more than 30 months in NSCLCs who harbor EGFR sensitive mutations, several study shows that sensitive mutations still exist after TKI resistance, because of the next generation TKIs(such as BIBW2992) are not avaliable at present, agents for met amplification(such as Crizotinib) are so expensive that many Chinese patients could not support. Thus, the investigators hypothesis that, after first line TKI treatment, the patients who developed TKI resistance could still benefit from second line TKI combined with chemotherapy.

Conditions

Carcinoma, Non-Small Cell Lung; EGFR Gene Mutation

Keywords

TKI; resistance; erlotinib; combined chemotherapy

Outcome Measures

Primary Outcomes (1)

• mean progression free survival(mPFS)

  mean progression free survival(mPFS) will be recorded in enroll patients who received second line gemcitabine platinum combined with erlotinib. mPFS should be measured before second line treatment, before the third combined chemotherapy, after the fourth combined chemotherapy, every 3 months during erlotinib treatment, mPFS should be measured up to two years or every time progression disease occurs within two years.

  after patients receive treatment, mPFS should be measured before the third cycle of chemotherapy, after the fourth cycle, mPFS should be measured every 3 months up to two years

Secondary Outcomes (2)

• mean overall survival(mOS)

  every 3 months up to 3 years, or until all the survival data is obtained

• 8 week overall response rate(8 week ORR)

  8 week ORR should be measured after enrollment, the exact time point should be the ninth week after combined chemotherapy

Study Arms (1)

experimental

EXPERIMENTAL

patients will received a 28 days gemcitabine platinum combined with erlotinib scheme(gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for 150mg/day, day 9-21 every cycle, after 4 cycles, erlotinib should be used daily), after 4 cycle of combined chemotherapy, patients will receive erlotinib for further treatment until progression disease.

Drug: Gemcitabine platinum combined with erlotinib

Interventions

Gemcitabine platinum combined with erlotinib DRUG

patients will received a 28 days gemcitabine platinum combined with erlotinib scheme, after 4 cycles combined chemotherapy, patients will receive erlotinib for maintain treatment until progression disease.Gemcitabine for day 1 and day 8, 1250mg/m2. Platinum for day 1, 75mg/m2. Erlotinib for day 9-21 during combined chemotherapy, 150mg/day, then erlotinib should be used daily until patients develop progression disease.

Also known as: Gemzar, Tarceva

experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• advanced non-small cell lung cancer, stage IIIB/IV
• non-squamous
• EGFR sensitive mutations, such as exon 19 del, or exon 21 L858R
• received first line TKIs treatment and developed TKI resistance
• ECOG 0-2

You may not qualify if:

• squamous non-small cell lung cancer
• patients have unstable brain metastasis, predict survival less than 8 weeks
• spinal-cord compression without evidence of stabilisation or treatment
• women who were pregnant or lactating; women with a positive or no available pregnancy test result at baseline
• patients have any unstable illness that could not receive further treatment

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Province Tumor Hospital

Changsha, Hunan, China

RECRUITING

Related Publications (2)

• Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. doi: 10.1016/S1470-2045(13)70254-7. Epub 2013 Jun 17.

  PMID: 23782814 RESULT

• Suda K, Mizuuchi H, Maehara Y, Mitsudomi T. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny. Cancer Metastasis Rev. 2012 Dec;31(3-4):807-14. doi: 10.1007/s10555-012-9391-7.

  PMID: 22736441 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Nong Yang, MD

  Hunan Province Tumor Hospital

  STUDY CHAIR

Central Study Contacts

Nong Yang, MD

CONTACT

+86 731 89762323; yangnong0217@163.com

Ming Zhou, MD

CONTACT

+86 731 89762320; zhouming243@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: HunanPTH

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 28, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2024
• Study Completion: December 12, 2025
• Last Updated: December 27, 2023

Record last verified: 2023-12

Locations

CN (1)