- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01749072
Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients
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
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Mengzhao Wang, MD
- Phone Number: +86 010-69155039
- Email: mengzhaowang@sina.com
Study Contact Backup
- Name: Jing Zhao, MD
- Phone Number: +86 010-69158206
- Email: pumchzj@sina.com
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100730
- Recruiting
- Department of Respiratory Medicine, Peking Union Medical College Hospital
-
Contact:
- Mengzhao Wang, MD
- Phone Number: +86 010-69155039
- Email: mengzhaowang@sina.com
-
Contact:
- Jing Zhao, MD
- Phone Number: +86 010-69158206
- Email: pumchzj@sina.com
-
Sub-Investigator:
- Wei Zhong, MD
-
Sub-Investigator:
- Jinmei Luo, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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;
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Gefitinib
Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects
|
Gefitinib 250mg once per day until the progression disease or intolerant side effects
Other Names:
|
Other: 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
|
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;
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: up to 52 weeks (about one year)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Up to 100 weeks
|
From date of randomization until the date of death from any cause, assessed up to 100 weeks.
|
Up to 100 weeks
|
objective response rate
Time Frame: up to 9 weeks
|
The objective response rate includes the complete remission and partial remission rate.
|
up to 9 weeks
|
the score of functional assessment of cancer treatment-lung (FACT-L)
Time Frame: Up to 100 weeks
|
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
|
Number of participants with adverse events
Time Frame: Up to six months
|
The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).
|
Up to six months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Mengzhao Wang, MD, Department of Respiratory Medicine, Peking Unoin Medical College Hospital
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Protein Kinase Inhibitors
- Ifosfamide
- Gefitinib
- Vinorelbine
Other Study ID Numbers
- PUMCH-S464
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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