Non-small Cell Lung CancerPhase 2NCT01749072
Vinorelbine-ifosfamide Versus Gefitinib for EGFR Gene Mutation Negative Non-small Cell Lung Cancer Patients
A Phase 2 study testing Gefitinib group and Vinorelbine, Ifosfamide, Mesna in people with Non-small Cell Lung Cancer and Effects of Chemotherapy, run by Peking Union Medical College Hospital at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-small Cell Lung Cancer, Effects of Chemotherapy
- What is being tested?
- Gefitinib group and Vinorelbine, Ifosfamide, Mesna
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteChina
- Study dates
- Dec 2012to Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 11Show fewer
- 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;
Who cannot join
- 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;
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Respiratory Medicine, Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Mengzhao Wang, MD, 010-69155039 ext. +86, mengzhaowang@sina.com
Jing Zhao, MD, 010-69158206 ext. +86, pumchzj@sina.com
About this study
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
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.
Read the 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.
- Being tested
- Gefitinib group, Vinorelbine, Ifosfamide, Mesna
- Keywords
- non small cell lung cancer, chemotherapy, gefitinib, vinorelbine, ifosfamide
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gefitinib groupDrug
Also called Gefitinib (Iressa)
Gefitinib 250mg once per day until the progression disease or intolerant side effects
Vinorelbine, Ifosfamide, MesnaDrug
Also called VI group
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;
| Study group | Role | What they receive |
|---|---|---|
| Gefitinib | Other | Gefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects Receives: Drug: Gefitinib group |
| Vinorelbine-Ifosfamide | Other | 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 Receives: Drug: Vinorelbine, Ifosfamide, Mesna |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 52 weeks (about one year)
Secondary outcomes (4)
Overall survival
From date of randomization until the date of death from any cause, assessed up to 100 weeks.
Measured: Up to 100 weeks
objective response rate
The objective response rate includes the complete remission and partial remission rate.
Measured: up to 9 weeks
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)
Measured: Up to 100 weeks
Number of participants with adverse events
The adverse events are assessed by National Cancer Institute-Common Toxicity Criteria (Version 3.0) (NCI-CTC).
Measured: Up to six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionDec 2016 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mengzhao Wang, MD, Principal investigator, Department of Respiratory Medicine, Peking Unoin Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01749072
- Sponsor's protocol ID
- PUMCH-S464
- Status last verified
- Dec 2012
- First submitted
- 11 Dec 2012
- Last updated
- 13 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 3028661Holoye 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.
PubMed 2156418Masters 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.
PubMed 9060524Bell 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.
PubMed 16204011Hirsch 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.
PubMed 17075123
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01749072
- Acronym / sponsor ID
- PUMCH-S464
- Keywords
- non small cell lung cancer, chemotherapy, gefitinib, vinorelbine, ifosfamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 13 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gefitinib | Other | Drug: Gefitinib groupGefitinib group Gefitinib (Iressa) 250mg once per day until progression disease or intolerant side effects |
| Vinorelbine-Ifosfamide | Other | Drug: Vinorelbine, Ifosfamide, MesnaVI 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gefitinib groupAlso: Gefitinib (Iressa)Gefitinib 250mg once per day until the progression disease or intolerant side effects | Drug | Gefitinib |
| Vinorelbine, Ifosfamide, MesnaAlso: VI groupVinorelbine 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; | Drug | Vinorelbine-Ifosfamide |
Primary outcome
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.
4 secondary outcomes
Overall survival
Time frame: Up to 100 weeks
objective response rate
Time frame: up to 9 weeks
the score of functional assessment of cancer treatment-lung (FACT-L)
Time frame: Up to 100 weeks
Number of participants with adverse events
Time frame: Up to six months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2012.
- Results publication: PubMed 3028661Thatcher 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.
- Results publication: PubMed 2156418Holoye 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.
- Results publication: PubMed 9060524Masters 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.
- Results publication: PubMed 16204011Bell 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.
- Results publication: PubMed 17075123Hirsch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mengzhao Wang, MD principal investigator
Department of Respiratory Medicine, Peking Unoin Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gefitinib group and Vinorelbine, Ifosfamide, Mesna in people with Non-small Cell Lung Cancer and Effects of Chemotherapy, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mengzhao Wang, MD (010-69155039 ext. +86, mengzhaowang@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: up to 52 weeks (about one year)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01749072, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2012.