Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients

NCT ID: NCT01749072

Last Updated: 2012-12-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2017-12-31

Brief Summary

In the National Comprehensive Cancer Network (NCCN) guideline for NSCLC, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is recommended as the third-line treatment for EGFR gene mutation negative NSCLC patients who failed to the first-line platinum doublet chemotherapy [i.e. paclitaxel-carboplatin (PC) or gemcitabine-cisplatin (GP)] and the second-line chemotherapy with docetaxel or pemetrexed. But as we know, if patients had no EGFR gene mutation, EGFR-TKI treatment is not effective. The overall survival is short and the objective response rate is low. As for EGFR gene wild type patients with good performance status, besides EGFR-TKI treatment, other first generation cytotoxic drugs i.e. vinorelbine or ifosfamide maybe an alternative treatment. So the purpose of this clinical trial is to compare the effectiveness and safety of vinorelbine-ifosfamide with gefitinib in advanced or metastatic EGFR gene mutation negative NSCLC patients.

Detailed Description

Ifosfamide is a first generation cytotoxic drug to treat NSCLC. Phase Ⅱ studies demonstrated that single-agent ifosfamide administrated by various schedules produces response rates of 15-29%, with media survival times of 5-7 months. Ifosfamide has also been used in various combination regimens to treat NSCLC, including platinum based and non-platinum regimens. But in refractory NSCLC patients platinum and some third generation cytotoxic drugs have been used before. So in this study, ifosfamide is combined with vinorelbine. In previous study, Masters reported the objective response rate was 40% and the median survival duration was 50 weeks, with a 1-year survival rate of 48% with vinorelbine-ifosfamide regimen [Vinorelbine 15 mg/m2 on days 1-3, and ifosfamide 2.0g/m2 on days 1-3 with granulocyte-colony stimulating factor (G-CSF) support]. The dose limiting toxicity (DLT) of this regimen is myelosuppression. In our experience, the regimen of vinorelbine 25mg/m2 d1, d8 and ifosfamide 1.25g/m2 d1-d3 with Mesna uroprotection is safe in Chinese population and the objective response rate is about 7% (data not published).

Gefitinib is the first small molecule inhibitor that has directed activity towards EGFR and has shown appreciable response rates in phase Ⅱ trials of patients with previously treated advanced NSCLC. In the posterior analysis of Iressa Dose Evaluation in Advanced Lung Cancer (IDEAL) and IRESSA Survival Evaluation in Lung Cancer (ISEL) trials, the response rate with gefitinib ranges from 2.6% to 10% in wild-type EGFR gene NSCLC patients.

Conditions

Non-small Cell Lung Cancer; Effects of Chemotherapy

Keywords

non small cell lung cancer; chemotherapy; gefitinib; vinorelbine; ifosfamide

Study Design

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

Study Groups

Gefitinib

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

Group Type: OTHER

Gefitinib group

Intervention Type: DRUG

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

Vinorelbine-Ifosfamide

VI group Vinorelbine 25mg/m2 d1,d8;Ifosfamide 1.25g/m2 d1-d3(Usually Ifosfamide 2g d1-d3 with Mesna 400mg 0,4,8hours after Ifosfamide administration for 3 days);every 3 weeks;at least for 2-6 cycles depending on the progression disease or the patient's physical condition

Group Type: OTHER

Vinorelbine, Ifosfamide, Mesna

Intervention Type: DRUG

Vinorelbine 25mg/m2 d1,d8; Ifosfamide 1.25g/m1 d1-d3 (Usually 2g d1-d3); Mesna 400mg 0,4,8 hours after Ifosfamide administration for uroprotection d1-d3;

Interventions

Gefitinib group

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

Intervention Type: DRUG

Vinorelbine, Ifosfamide, Mesna

Vinorelbine 25mg/m2 d1,d8; Ifosfamide 1.25g/m1 d1-d3 (Usually 2g d1-d3); Mesna 400mg 0,4,8 hours after Ifosfamide administration for uroprotection d1-d3;

Intervention Type: DRUG

Other Intervention Names

Gefitinib (Iressa); VI group

Eligibility Criteria

Inclusion Criteria

• age range:18-70 years old
• life expectancy more than 12 weeks
• histologically or cytologically confirmed inoperable 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;
• prior treatments include first-line platinum doublet chemotherapy i.e. PC or GP and second-line chemotherapy with docetaxel or pemetrexed;
• 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;

Exclusion Criteria

• prior treatments including any of the following drugs:gefitinib,vinorelbine and ifosfamide;
• 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 or surgery;
• pregnancy or breast feeding phase;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mengzhao Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Respiratory Medicine, Peking Unoin Medical College Hospital

Locations

Department of Respiratory Medicine, Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Mengzhao Wang, MD

Role: CONTACT

Phone: 010-69155039

Email: mengzhaowang@sina.com

Jing Zhao, MD

Role: CONTACT

Phone: 010-69158206

Email: pumchzj@sina.com

Facility Contacts

Mengzhao Wang, MD

Role: primary

Jing Zhao, MD

Role: backup

References

Thatcher N, Anderson H, Smith DB, Steward WP, Webb K, Hilton A, Rahman A. Ifosfamide by bolus as treatment for advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 1986;18 Suppl 2:S30-3. doi: 10.1007/BF00647448.

Reference Type: RESULT

PMID: 3028661 (View on PubMed)

Holoye PY, Glisson BS, Lee JS, Dhingra HM, Murphy WK, Umsawasdi T, Levy JK, Jeffries D, Raber MN, Hong WK. Ifosfamide with mesna uroprotection in the management of lung cancer. Am J Clin Oncol. 1990 Apr;13(2):148-55. doi: 10.1097/00000421-199004000-00012.

Reference Type: RESULT

PMID: 2156418 (View on PubMed)

Masters GA, Hoffman PC, Hsieh A, Drinkard LC, Mick R, Samuels BL, Guaspari A, Golomb HM, Vokes EE. Phase I study of vinorelbine and ifosfamide in advanced non-small-cell lung cancer. J Clin Oncol. 1997 Mar;15(3):884-92. doi: 10.1200/JCO.1997.15.3.884.

Reference Type: RESULT

PMID: 9060524 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16204011 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17075123 (View on PubMed)

Other Identifiers

PUMCH-S464

Identifier Type: -

Identifier Source: org_study_id