Gefitinib or Docetaxel as Second Line Therapy for Wild-type Epidermal Growth Factor Receptor (EGFR) NSCLC

NCT01755923 | Unknown Phase 2

• 1 other identifier: PUMCH-S466
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Gefitinib, the first EGFR-tyrosine kinase inhibitor (TKI) in the world was examined as monotherapy in two phase Ⅱ studies called IDEAL trials. Response rate with doses of 250mg and 500mg/day were similar, ranging from 10% to 18%. Posterior analysis demonstrated that patients with EGFR mutation had an improved response rate (RR) to gefitinib compared to wild-type patients (46% versus 10%). The early trials that evaluated EGFR-TKIs for the second- and third-line settings of advanced NSCLC did not select patients on the basis of any EGFR marker. The IEESSA Survival Evaluation in Lung Cancer (ISEL) trial evaluated the role of second-line gefitinib 250mg/day in 1692 patients with advanced NSCLC. Patients with EGFR mutations had higher RR than patients without (37.5% versus 2.6%). From the above results, the response rate in patients without EGFR gene mutation was obviously different (10% versus 2.6%). The methods used for detecting EGFR gene mutation was different, which might contribute to the difference of response rates. In IDEAL trial, EGFR gene mutation was detected by sequencing. But in ISEL trial, EGFR gene mutation was detected by ARMS. As we know, ARMS was more sensitive than sequencing in detecting EGFR gene mutation. That is to say, in IDEAL trials some EGFR mutant patients were misdiagnosed as wild-type patients, so the response rate was higher. Recently, Wu Yi-Long et al reported that relative abundance of EGFR mutations predicted benefit form gefitinib treatment for advanced non small cell lung cancer. The study cohort was all Chinese. In this study, the objective response rate in patients without EGFR mutation detected by ARMS was 16.1%, which was significantly higher than the response rate of docetaxel. But in 2012 American society of clinical oncology (ASCO) annual meeting, the Tailor study in which Italian NSCLC patients were enrolled demonstrated a clear superiority of docetaxel over erlotinib as second line treatment for patients without EGFR mutations in exons 19 or 21. So we wonder if the racial difference is the determinant factor. So the purpose of this trial is to compare the efficacy and safety of gefitinib with docetaxel as second-line therapy for advanced or metastatic Chinese NSCLC patients with wild-type EGFR.

Conditions

Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer; wild-type EGFR; gefitinib; docetaxel; second-line therapy

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 52 weeks.

  up to 52 weeks (about one year)

Secondary Outcomes (4)

• Overall survival

  Up to 100 weeks

• Objective response rate

  up to 9 weeks

• the score of functional assessment of cancer treatment-lung (FACT-L)

  up to 100 weeks

• Number of participants with adverse events

  Up to 6 months

Study Arms (2)

Gefitinib

EXPERIMENTAL

Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects

Drug: Gefitinib

Docetaxel

ACTIVE COMPARATOR

Docetaxel 75mg/m2,d1,every 3 weeks, at least 2-6 cycles depending on the progression disease or the patient's physical condition

Drug: Docetaxel

Interventions

Gefitinib DRUG

Gefitinib 250mg once per day until the progression disease or intolerant side effects

Also known as: Iressa

Gefitinib

Docetaxel DRUG

Docetaxel 75mg/m2 iv, d1,every 3 weeks, at least 2-6 cycles depending on the progression disease or the patient's physical condition

Also known as: Taxotere

Docetaxel

Eligibility Criteria

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

You may qualify if:

• Age more than 18 years old
• Life expectancy more than 12 weeks
• histologically or cytologically confirmed inoperable non-squamous NSCLC (stage ⅢB/Ⅳ)
• ineligible for curative radiotherapy
• no prior radiotherapy for the target lesions
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• previous treatment include first-line platinum doublet chemotherapy
• no EGFR gene mutation detected by Scorpions-ARMS
• at least one bidimensionally measurable or radiographically assessable lesion
• adequate bone marrow reserve
• adequate hepatic and renal function

You may not qualify if:

• prior treatments including any of the following drugs: gefitinib and docetaxel
• additional malignancies
• uncontrolled systemic disease
• any evidence of clinically active interstitial lung disease
• newly diagnosed central nervous system (CNS)metastasis and not treated by radiotherapy of surgery
• pregnancy or breast feeding phase

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Department of Respiratory Medicine, Peking Union Medical College Hospita

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (10)

• Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095-103. doi: 10.1200/JCO.2000.18.10.2095.

  PMID: 10811675 RESULT

• Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol. 2000 Jun;18(12):2354-62. doi: 10.1200/JCO.2000.18.12.2354.

  PMID: 10856094 RESULT

• Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. doi: 10.1200/JCO.2004.08.163.

  PMID: 15117980 RESULT

• Cufer T, Vrdoljak E, Gaafar R, Erensoy I, Pemberton K; SIGN Study Group. Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer. Anticancer Drugs. 2006 Apr;17(4):401-9. doi: 10.1097/01.cad.0000203381.99490.ab.

  PMID: 16549997 RESULT

• Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong RP, Baselga J. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003 Jun 15;21(12):2237-46. doi: 10.1200/JCO.2003.10.038. Epub 2003 May 14.

  PMID: 12748244 RESULT

• Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. doi: 10.1001/jama.290.16.2149.

  PMID: 14570950 RESULT

• Bell DW, Lynch TJ, Haserlat SM, Harris PL, Okimoto RA, Brannigan BW, Sgroi DC, Muir B, Riemenschneider MJ, Iacona RB, Krebs AD, Johnson DH, Giaccone G, Herbst RS, Manegold C, Fukuoka M, Kris MG, Baselga J, Ochs JS, Haber DA. Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol. 2005 Nov 1;23(31):8081-92. doi: 10.1200/JCO.2005.02.7078. Epub 2005 Oct 3.

  PMID: 16204011 RESULT

• Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. doi: 10.1056/NEJMoa050753.

  PMID: 16014882 RESULT

• Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37. doi: 10.1016/S0140-6736(05)67625-8.

  PMID: 16257339 RESULT

• Hirsch FR, Varella-Garcia M, Bunn PA Jr, Franklin WA, Dziadziuszko R, Thatcher N, Chang A, Parikh P, Pereira JR, Ciuleanu T, von Pawel J, Watkins C, Flannery A, Ellison G, Donald E, Knight L, Parums D, Botwood N, Holloway B. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol. 2006 Nov 1;24(31):5034-42. doi: 10.1200/JCO.2006.06.3958.

  PMID: 17075123 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; Docetaxel

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Mengzhao Wang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mengzhao Wang, MD

CONTACT

010-69155039; mengzhaowang@sina.com

Jing Zhao, MD

CONTACT

010-69158206; pumchzj@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2012
• First Posted: December 24, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: December 24, 2012

Record last verified: 2012-12

Locations

CN (1)