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

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase Ⅱ Randomized Clinical Trial Comparing Vinorelbine-ifosfamide With Gefitinib as Third-line Treatment in Advanced EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01749072
• Other study ID #: PUMCH-S464
• Status: Recruiting
• Phase: Phase 2
• First received: December 11, 2012
• Last updated: December 12, 2012
• Start date: December 2012
• Est. completion date: December 2017

Study information

• Verified date: December 2012
• Source: Peking Union Medical College Hospital
• Contact: Mengzhao Wang, MD
• Phone: 010-69155039
• Email: mengzhaowang[@]sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• age range:18-70 years old

• life expectancy more than 12 weeks

• histologically or cytologically confirmed inoperable NSCLC (stage ?B/?)

• 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;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Effects of Chemotherapy
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Gefitinib group
Gefitinib 250mg once per day until the progression disease or intolerant side effects
• 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;

Locations

Country	Name	City	State
China	Department of Respiratory Medicine, Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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 recept — View Citation

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 outcom — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Overall survival	From date of randomization until the date of death from any cause, assessed up to 100 weeks.	Up to 100 weeks	No
Secondary	objective response rate	The objective response rate includes the complete remission and partial remission rate.	up to 9 weeks	No
Secondary	the score of functional assessment of cancer treatment-lung (FACT-L)	FACL-L is assessed at different time points.(Date of randomization, 1 week after chemotherapy/EGFR-TKI, every cycle of chemotherapy/EGFR-TKI, every month of EGFR-TKI treatment/observation, up to 100 weeks)	Up to 100 weeks	No
Secondary	Number of participants with adverse events	The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).	Up to six months	Yes