Non-Small Cell Lung CancerPhase 1NCT00870532
Study of Combination of Metronomic Oral Vinorelbine and Sorafenib in Patients With Advanced Non-small Cell Lung Cancer
A Phase 1 study testing oral vinorelbine and sorafenib in people with Non-Small Cell Lung Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
Targeting the blood supply of cancer, called anti-angiogenesis is a new but proven treatment strategy. There are two ways of achieving this effect. The first way to specifically target the molecular pathways that promote new blood vessel formation in 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?
- oral vinorelbine and sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteSingapore
- Study dates
- Jun 2008to Sep 2013
- 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
- Patients must have histologically or cytologically confirmed NSCLC
- At least one or 2 prior lines of chemotherapy, including oral EGFR tyrosine-kinase inhibitor for metastatic disease or locally advanced unresectable disease. There should be at least 4 weeks since prior chemotherapy or radiation therapy; patients who decline conventional chemotherapy or oral EGFR tyrosine-kinase inhibitor as salvage 2nd or 3rd line treatment are also eligible.
- Minimum body-surface area (BSA) of 1.4 m2 at point of recruitment. This is a safeguard against recruiting small-built patients who may experience adverse reaction on absolute dosing of oral vinorelbine. At this body surface area, the maximum dosing of oral vinorelbine at 120 mg/week is equivalent to 86 mg/m2/week for a patient with BSA of 1.4 m2.
- Age >21 years
- ECOG performance status <2 (Karnofsky >60%)
- Patients must have normal organ and marrow function as defined here: leukocytes >3,000/mcL, absolute neutrophil count >1,500/mcL, platelet count > 100,000/mcL, serum bilirubin within normal institutional limits, AST(SGOT)/ALT(SGPT) <2.5 X upper limit of normal, and creatinine within normal institutional limits or creatinine clearance >60 mL/min/1.73 m2 for patients. These tests must be done within 1 week of study treatment.
- 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 prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients receiving any other investigational agents
- Patients with known 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
- 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: phenytoin, carbamazepine, barbiturates, rifampicin, imidazole antifungals (such as ketoconazole, fluconazole, itraconazole, metronidazole), omeprazole and ritonavir. Patients who are taking gastric acid-lowering agents such as H2 antagonist or antacids will be evaluated regarding the need to continue with these medications. If discontinuation of these medications is medically contraindicated, the patient will be excluded as these agents are known to lower the solubility of sorafenib and hence may limit their efficacy.
- Significant malabsorption syndrome or disease affecting the gastro-intestinal tract function
Show all 14Show fewer
- Significant peripheral or autonomic neuropathy affecting sensation or bowel motility
- 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
- Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg despite optimal management
- Pregnancy or breast-feeding or women of childbearing potential not using effective contraception
- Evidence or history of bleeding diathesis or coagulopathy
- Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
- Pulmonary hemorrhage/bleeding event >CTCAE grade 2 within 4 weeks of recruitment
- Any other hemorrhage/bleeding event >CTCAE grade 3 within 4 weeks of recruitment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Study of Metronomic Oral Vinorelbine in Combination With Sorafenib in Advanced Non-small Cell Lung Cancer a) A Phase I Dose-finding Study of the Combination of Metronomic Oral Vinorelbine and Sorafenib b) Pharmacokinetics Profiling of the Combination of Metronomic Oral Vinorelbine and Sorafenib at MTD
Targeting the blood supply of cancer, called anti-angiogenesis is a new but proven treatment strategy. There are two ways of achieving this effect. The first way to specifically target the molecular pathways that promote new blood vessel formation in cancer. An example of such an agent is sorafenib, which is an oral agent and which is already in use worldwide for the treatment of kidney and liver cancers. The second way is to target the cells lining the blood vessels by using low dose of chemotherapy agents administered at frequent intervals. This strategy is called metronomic chemotherapy. It is possible that combining agents like sorafenib and metronomic chemotherapy may further enhance anti-cancer effects. This study aims to determine the optimal way of combining oral vinorelbine in metronomic doses and sorafenib. Oral vinorelbine is a chemotherapy agent that is already approved for use in cancer treatment such as lung cancer. By combining both oral anti-cancer agents to optimize their anti-angiogenic effects in this study, the potential benefit to the patients can be tremendous and far-reaching. Special radiologic imagings and blood tests will be incorporated into this study to help further the understanding of the anti-angiogenic processes of both agents.
Read the detailed description
Phase I Dose-finding study: The patients will be divided into 3 cohorts (15 patients per cohort), each cohort receiving a fixed metronomic (thrice a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, and 120 mg/week respectively. Each patient within each cohort will receive a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, the dose of sorafenib will be escalated to 400 mg bid for another 4 weeks, 600 mg bid for 4 weeks and then finally 800 mg bid. We should arrive at 3 different MTDs from the 3 cohorts.
Once the MTD has been determined for each cohort, we will recruit an additional 12 patients for each cohort and study the PK profile of both drugs. The 12 patients in each cohort will be sequentially alternated to group 1 or group 2 treatment schedules. Group 1 (N=6 patients in each cohort) will receive vinorelbine three times per week starting on Monday (Day 1) followed by Wednesday (Day 3) and Friday (Day 5). In the subsequent weeks vinorelbine will be given on the same working days (i.e. Monday, Wednesday and Friday). The first PK profile of vinorelbine (without concomitant sorafenib) will be determined on Day 15 under steady state conditions.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- oral vinorelbine, sorafenib
- Keywords
- Phase I, Combination, Anti-angiogenic, Sorafenib, Metronomic oral vinorelbine
- 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.
oral vinorelbineDrug
Also called Navelbine Oral
The patients will be divided into 3 cohorts (15 patients per cohort), each cohort receiving a fixed metronomic (thrice a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, and 120 mg/week respectively. We should arrive at 3 different MTDs from the 3 cohorts.
sorafenibDrug
Also called Nexavar
Each patient within each cohort will receive a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, the dose of sorafenib will be escalated to 400 mg bid for another 4 weeks, 600 mg bid for 4 weeks and then finally 800 mg bid. We should arrive at 3 different MTDs from the 3 cohorts.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 60 mg/week of vinorelbine + sorafenib Receives: Drug: oral vinorelbine; Drug: sorafenib |
| 2 | Experimental | 90 mg/week of vinorelbine + sorafenib Receives: Drug: oral vinorelbine; Drug: sorafenib |
| 3 | Experimental | 120 mg/week of vinorelbine + sorafenib Receives: Drug: oral vinorelbine; Drug: sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
to determine the optimal combination of metronomic oral vinorelbine with sorafenib to achieve anti-angiogenic and hence anti-tumour effect in patients with advanced NSCLC
Measured: every 1-2 monthly with DCE-MR and circulating endothelial cells apart from routine CT scans
Secondary outcomes (1)
To determine the response rate to the combination of metronomic oral vinorelbine and sorafenib in advanced NSCLC
Measured: CT scan every 2 months while on treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2009 (estimated)
- Study startJun 2008
- Primary completionAug 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eng-Huat Tan, National Cancer Centre, Singapore
- Investigators
- Eng-Huat Tan, MD, Principal investigator, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00870532
- Sponsor's protocol ID
- 08-3-LUN
- Status last verified
- Nov 2013
- First submitted
- 9 Jun 2008
- Last updated
- 4 Nov 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Metronomic Oral Vinorelbine in Combination With Sorafenib in Advanced Non-small Cell Lung Cancer a) A Phase I Dose-finding Study of the Combination of Metronomic Oral Vinorelbine and Sorafenib b) Pharmacokinetics Profiling of the Combination of Metronomic Oral Vinorelbine and Sorafenib at MTD
- ClinicalTrials.gov ID
- NCT00870532
- Acronym / sponsor ID
- 08-3-LUN
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Phase I, Combination, Anti-angiogenic, Sorafenib, Metronomic oral vinorelbine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 27 Mar 2009 (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.
Targeting the blood supply of cancer, called anti-angiogenesis is a new but proven treatment strategy. There are two ways of achieving this effect. The first way to specifically target the molecular pathways that promote new blood vessel formation in cancer. An example of such an agent is sorafenib, which is an oral agent and which is already in use worldwide for the treatment of kidney and liver cancers. The second way is to target the cells lining the blood vessels by using low dose of chemotherapy agents administered at frequent intervals. This strategy is called metronomic chemotherapy. It is possible that combining agents like sorafenib and metronomic chemotherapy may further enhance anti-cancer effects. This study aims to determine the optimal way of combining oral vinorelbine in metronomic doses and sorafenib. Oral vinorelbine is a chemotherapy agent that is already approved for use in cancer treatment such as lung cancer. By combining both oral anti-cancer agents to optimize their anti-angiogenic effects in this study, the potential benefit to the patients can be tremendous and far-reaching. Special radiologic imagings and blood tests will be incorporated into this study to help further the understanding of the anti-angiogenic processes of both agents.
Detailed description
Phase I Dose-finding study: The patients will be divided into 3 cohorts (15 patients per cohort), each cohort receiving a fixed metronomic (thrice a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, and 120 mg/week respectively. Each patient within each cohort will receive a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, the dose of sorafenib will be escalated to 400 mg bid for another 4 weeks, 600 mg bid for 4 weeks and then finally 800 mg bid. We should arrive at 3 different MTDs from the 3 cohorts.
Once the MTD has been determined for each cohort, we will recruit an additional 12 patients for each cohort and study the PK profile of both drugs. The 12 patients in each cohort will be sequentially alternated to group 1 or group 2 treatment schedules. Group 1 (N=6 patients in each cohort) will receive vinorelbine three times per week starting on Monday (Day 1) followed by Wednesday (Day 3) and Friday (Day 5). In the subsequent weeks vinorelbine will be given on the same working days (i.e. Monday, Wednesday and Friday). The first PK profile of vinorelbine (without concomitant sorafenib) will be determined on Day 15 under steady state conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: oral vinorelbine, Drug: sorafenib60 mg/week of vinorelbine + sorafenib |
| 2 | Experimental | Drug: oral vinorelbine, Drug: sorafenib90 mg/week of vinorelbine + sorafenib |
| 3 | Experimental | Drug: oral vinorelbine, Drug: sorafenib120 mg/week of vinorelbine + sorafenib |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have histologically or cytologically confirmed NSCLC
- At least one or 2 prior lines of chemotherapy, including oral EGFR tyrosine-kinase inhibitor for metastatic disease or locally advanced unresectable disease. There should be at least 4 weeks since prior chemotherapy or radiation therapy; patients who decline conventional chemotherapy or oral EGFR tyrosine-kinase inhibitor as salvage 2nd or 3rd line treatment are also eligible.
- Minimum body-surface area (BSA) of 1.4 m2 at point of recruitment. This is a safeguard against recruiting small-built patients who may experience adverse reaction on absolute dosing of oral vinorelbine. At this body surface area, the maximum dosing of oral vinorelbine at 120 mg/week is equivalent to 86 mg/m2/week for a patient with BSA of 1.4 m2.
- Age >21 years
- ECOG performance status <2 (Karnofsky >60%)
Key exclusion criteria (14 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients receiving any other investigational agents
- Patients with known 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
- 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: phenytoin, carbamazepine, barbiturates, rifampicin, imidazole antifungals (such as ketoconazole, fluconazole, itraconazole, metronidazole), omeprazole and ritonavir. Patients who are taking gastric acid-lowering agents such as H2 antagonist or antacids will be evaluated regarding the need to continue with these medications. If discontinuation of these medications is medically contraindicated, the patient will be excluded as these agents are known to lower the solubility of sorafenib and hence may limit their efficacy.
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 |
|---|---|---|
| oral vinorelbineAlso: Navelbine OralThe patients will be divided into 3 cohorts (15 patients per cohort), each cohort receiving a fixed metronomic (thrice a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, and 120 mg/week respectively. We should arrive at 3 different MTDs from the 3 cohorts. | Drug | 1, 2, 3 |
| sorafenibAlso: NexavarEach patient within each cohort will receive a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, the dose of sorafenib will be escalated to 400 mg bid for another 4 weeks, 600 mg bid for 4 weeks and then finally 800 mg bid. We should arrive at 3 different MTDs from the 3 cohorts. | Drug | 1, 2, 3 |
Primary outcome
to determine the optimal combination of metronomic oral vinorelbine with sorafenib to achieve anti-angiogenic and hence anti-tumour effect in patients with advanced NSCLC
Time frame: every 1-2 monthly with DCE-MR and circulating endothelial cells apart from routine CT scans
1 secondary outcome
To determine the response rate to the combination of metronomic oral vinorelbine and sorafenib in advanced NSCLC
Time frame: CT scan every 2 months while on treatment
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 4 Nov 2013.
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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.
Eng-Huat Tan, MD principal investigator
National Cancer Centre, 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 oral vinorelbine and sorafenib 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 7 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 4 Nov 2013. 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?
to determine the optimal combination of metronomic oral vinorelbine with sorafenib to achieve anti-angiogenic and hence anti-tumour effect in patients with advanced NSCLC (time frame: every 1-2 monthly with DCE-MR and circulating endothelial cells apart from routine CT scans). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2013.