Non-Small Cell Lung CancerPhase 1NCT00702182
Study of Oral Vinorelbine and Erlotinib in Non-Small Cell Lung Cancer
A Phase 1 study testing Vinorelbine (Navelbine) and Erlotinib in people with Non-Small Cell Lung Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
The purpose of this study is to define the schedule and dose of oral vinorelbine (Navelbine) to be used with erlotinib in non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Vinorelbine (Navelbine) and Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSingapore
- Study dates
- Apr 2008to Oct 2012
- Phase
- Phase 1
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed NSCLC
- At least one or two prior lines of chemotherapy for metastatic disease or locally advanced unresectable disease. There should be at least 4 weeks since prior chemotherapy or radiation therapy or 6 weeks if the last regimen included BCNU or mitomycin C
- Age > 21 years.
- ECOG performance status <2 (Karnofsky >60%, see Appendix A).
- Life expectancy of greater than 3 months
- Patients must have normal organ and marrow function as defined below:
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- leukocytes >3,000/mcL
- absolute neutrophil count >1,500/mcL
- platelets >100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) <2.5 X institutional ULN
- creatinine within normal institutional limits OR
- creatinine clearance >60 mL/min/1.73 m2
- The effects of Oral Vinorelbine on the developing human fetus are unknown. For this reason and because vinca alkaloids as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients who have received previous vinorelbine or oral EGFR tyrosine kinase inhibitors
- Patients with progressive brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However patients are eligible if they have brain metastases that have been treated with whole brain radiotherapy and are stable and not on corticosteroids.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Oral Vinorelbine or other agents used in study.
- Prior and / or concomitant treatment with drugs known to induce or inhibit cytochrome P450 3A4, CYP1A1 \& CYP1A2 : phenytoin, carbamazepine, barbiturates, rifampicin, imidazole antifungals (such as ketoconazole, fluconazole, itraconazole, metronidazole), omeprazole and ritonavir
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- Significant malabsorption syndrome or disease affecting the gastro-intestinal tract function
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnancy or breast feeding or women of child-bearing potential not using effective contraception,
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Oral Vinorelbine. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- History of organ allograft
- Patients with evidence or history of bleeding diatheses or coagulopathy
- Serious, non-healing wound, ulcer, or bone fracture
- Because of interaction risk on CYP3A4, patients with concomitant treatments with vitamin K antagonists such as phenprocoumon or warfarin or heparin or heparinoids should be excluded
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Study of Oral Vinorelbine in Combination With Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules
The purpose of this study is to define the schedule and dose of oral vinorelbine (Navelbine) to be used with erlotinib in non-small cell lung cancer.
Read the detailed description
Additive or supraadditive activity of an EGFR TK-I with vinorelbine has been demonstrated in-vitro. Clinical synergism has also been described between gefitinib and vinorelbine in NSCLC. The use of cytotoxics in a metronomic schedule has not been well investigated in the clinical setting despite emerging pre-clinical data. Using an established oral cytotoxic such as oral vinorelbine in a metronomic dose-schedule is attractive due to the oral route of administration. Preclinical studies have shown that by using cytotoxics in a low-dose protracted manner, endothelial cells are preferentially affected via inhibition of proliferation and induction of apoptosis. In addition to this anti-angiogenic mechanism, an anti-vasculogenic process may also be involved that acts by reducing circulating endothelial progenitor mobilization and viability. Moreover, it has also been shown that tumours that were selected for high levels of acquired resistance to cytotoxics can be induced to respond by using metronomic doses of chemotherapy.
Continuous administration of metronomic oral vinorelbine, given three times a week, has been reported as feasible and well tolerated at doses up to 180 mg total dose per week. Early results showed activity against refractory solid tumors such as renal cancer, NSCLC, ovarian cancer, prostate cancer, unknown primary and Kaposi sarcoma.
This phase I study combines erlotinib and oral vinorelbine on two different schedules. The conventional schedule vinorelbine (CSV) aims to determine the MTD of conventional schedule of oral vinorelbine given on days 1 and 8 every 21 days plus daily erlotinib and the metronomic schedule vinorelbine (MSV) aims to determine the optimal metronomic dose of vinorelbine given 3 times a week plus daily erlotinib.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Vinorelbine (Navelbine), Erlotinib
- Keywords
- Lung Cancer, Vinorelbine, Erlotinib, Phase 1
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vinorelbine (Navelbine)Drug
Also called Navelbine
Conventional Schedule Oral Vinorelbine on day 1 and day 8 of a 21 day schedule
Vinorelbine (Navelbine)Drug
Also called Navelbine
Metronomic Schedule Oral Vinorelbine 3 times a week
ErlotinibDrug
Also called Tarceva
Daily Oral Erlotinib 100 mg
| Study group | Role | What they receive |
|---|---|---|
| Conventional Vinorelbine, Erlotinib | Experimental | Escalating doses of vinorelbine on Day 1 and Day 8 of 21 Day cycle; Erlotinib 100 mg OD Receives: Drug: Vinorelbine (Navelbine); Drug: Erlotinib |
| Metronomic Vinorelbine, Erlotinib | Experimental | Escalating doses of vinorelbine TIW; erlotinib 100 mg OD Receives: Drug: Vinorelbine (Navelbine); Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Define the recommended dose of oral navelbine with erlotinib
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2008 (estimated)
- Study startApr 2008
- Primary completionApr 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wan-Teck Darren Lim, National Cancer Centre, Singapore
- Investigators
- Wan-Teck Lim, MD, Principal investigator, National Cancer Center Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00702182
- Sponsor's protocol ID
- EPCTG-VEP1
- Status last verified
- Oct 2012
- First submitted
- 19 Jun 2008
- Last updated
- 19 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Sutiman N, Zhang Z, Tan EH, Ang MK, Tan SW, Toh CK, Ng QS, Chowbay B, Lim WT. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules. PLoS One. 2016 May 2;11(5):e0154316. doi: 10.1371/journal.pone.0154316. eCollection 2016.
PubMed 27135612
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Oral Vinorelbine in Combination With Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules
- ClinicalTrials.gov ID
- NCT00702182
- Acronym / sponsor ID
- EPCTG-VEP1
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Lung Cancer, Vinorelbine, Erlotinib, Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Apr 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 20 Jun 2008 (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.
The purpose of this study is to define the schedule and dose of oral vinorelbine (Navelbine) to be used with erlotinib in non-small cell lung cancer.
Detailed description
Additive or supraadditive activity of an EGFR TK-I with vinorelbine has been demonstrated in-vitro. Clinical synergism has also been described between gefitinib and vinorelbine in NSCLC. The use of cytotoxics in a metronomic schedule has not been well investigated in the clinical setting despite emerging pre-clinical data. Using an established oral cytotoxic such as oral vinorelbine in a metronomic dose-schedule is attractive due to the oral route of administration. Preclinical studies have shown that by using cytotoxics in a low-dose protracted manner, endothelial cells are preferentially affected via inhibition of proliferation and induction of apoptosis. In addition to this anti-angiogenic mechanism, an anti-vasculogenic process may also be involved that acts by reducing circulating endothelial progenitor mobilization and viability. Moreover, it has also been shown that tumours that were selected for high levels of acquired resistance to cytotoxics can be induced to respond by using metronomic doses of chemotherapy.
Continuous administration of metronomic oral vinorelbine, given three times a week, has been reported as feasible and well tolerated at doses up to 180 mg total dose per week. Early results showed activity against refractory solid tumors such as renal cancer, NSCLC, ovarian cancer, prostate cancer, unknown primary and Kaposi sarcoma.
This phase I study combines erlotinib and oral vinorelbine on two different schedules. The conventional schedule vinorelbine (CSV) aims to determine the MTD of conventional schedule of oral vinorelbine given on days 1 and 8 every 21 days plus daily erlotinib and the metronomic schedule vinorelbine (MSV) aims to determine the optimal metronomic dose of vinorelbine given 3 times a week plus daily erlotinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional Vinorelbine, Erlotinib | Experimental | Drug: Vinorelbine (Navelbine), Drug: ErlotinibEscalating doses of vinorelbine on Day 1 and Day 8 of 21 Day cycle; Erlotinib 100 mg OD |
| Metronomic Vinorelbine, Erlotinib | Experimental | Drug: Vinorelbine (Navelbine), Drug: ErlotinibEscalating doses of vinorelbine TIW; erlotinib 100 mg OD |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically or cytologically confirmed NSCLC
- At least one or two prior lines of chemotherapy for metastatic disease or locally advanced unresectable disease. There should be at least 4 weeks since prior chemotherapy or radiation therapy or 6 weeks if the last regimen included BCNU or mitomycin C
- Age > 21 years.
- ECOG performance status <2 (Karnofsky >60%, see Appendix A).
- Life expectancy of greater than 3 months
Key exclusion criteria (14 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients who have received previous vinorelbine or oral EGFR tyrosine kinase inhibitors
- Patients with progressive brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However patients are eligible if they have brain metastases that have been treated with whole brain radiotherapy and are stable and not on corticosteroids.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Oral Vinorelbine or other agents used in study.
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 |
|---|---|---|
| Vinorelbine (Navelbine)Also: NavelbineConventional Schedule Oral Vinorelbine on day 1 and day 8 of a 21 day schedule | Drug | Conventional Vinorelbine, Erlotinib |
| Vinorelbine (Navelbine)Also: NavelbineMetronomic Schedule Oral Vinorelbine 3 times a week | Drug | Metronomic Vinorelbine, Erlotinib |
| ErlotinibAlso: TarcevaDaily Oral Erlotinib 100 mg | Drug | Conventional Vinorelbine, Erlotinib, Metronomic Vinorelbine, Erlotinib |
Primary outcome
Define the recommended dose of oral navelbine with erlotinib
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2012.
- Derived from this study: PubMed 27135612Sutiman N, Zhang Z, Tan EH, Ang MK, Tan SW, Toh CK, Ng QS, Chowbay B, Lim WT. Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules. PLoS One. 2016 May 2;11(5):e0154316. doi: 10.1371/journal.pone.0154316. eCollection 2016.
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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.
Wan-Teck Lim, MD principal investigator
National Cancer Center Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vinorelbine (Navelbine) and Erlotinib in people with Non-Small Cell Lung Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 15 inclusion and 14 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: finished, as of the sponsor's last update on 19 Oct 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 Singapore. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Define the recommended dose of oral navelbine with erlotinib (time frame: 3 weeks). 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 NCT00702182, which also lists 1 linked publication.
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 19 Oct 2012.