Neoplasms, BreastPhase 1NCT00258050
To Examine The Effects Of Lapatinib On Orally And Intravenously Administered Midazolam In Cancer Patients
A Phase 1 study testing Midazolam and Lapatinib in people with Neoplasms, Breast, run by GlaxoSmithKline at 2 sites in United States.
Trial summary
To characterize the effect of repeat oral dose of lapatinib treatment on the pharmacokinetics of a single oral and single intravenous dose of midazolam in adult cancer patients. Also to assess the safety and tolerability of chronic oral lapatinib therapy in cancer patients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- Midazolam and Lapatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Nov 2005to 8 Feb 2007
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed, solid tumor refractory to standard therapy.
- Tumor for which there is no standard therapy.
- Able to swallow and retain oral medication.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
- Provided written informed consent.
- Adequate bone marrow function.
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- Serum creatinine is less than or equal to 1.5 mg/dL.
- Calculated creatinine clearance is greater than or equal to 60 ml/min based on Cockcroft and Gault.
- Total bilirubin is greater than or equal to the upper limit of normal of institutional values.
- Aspartate and alanine transaminase is less than or equal to 3 times the upper limit of the institutional values.
- Have a left ventricular ejection fraction (LVEF) greater than or equal to 40% based on electrocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
- Resting oxygen saturations of greater than 90%.
Who cannot join
- Pregnant or lactating female.
- Have malabsorption syndrome, a disease affecting gastrointestinal function.
- Resection of the stomach or small bowel.
- Evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease.
- Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product.
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- Use of anilinoquinazolines, such as gefitinib [Iressa™], erlotinib [Tarceva™].
- Immediate or delayed hypersensitivity reaction to midazolam or any component of the formulation, including benzyl alcohol (cross-sensitivity with other benzodiazepines may exist).
- Has narrow-angle glaucoma which is a contraindication to midazolam use.
- Has received treatment with any investigational drug in the previous 4 weeks.
- Received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the past 14 days, with the exception of mitomycin C within the past 6 weeks.
- Currently receiving amiodarone or has received amiodarone in the 6 months prior to screening.
- Is taking regular doses of opiates that in the opinion of the investigator would put the patient at risk of clinically significant respiratory compromise when midazolam is administered.
- Physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- Has Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Clinically significant electrocardiogram (ECG) abnormality.
- Clinically assessed to have inadequate venous access for protocol-related blood draws.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
GSK Investigational Site
Chapel Hill, North Carolina, 27599
GSK Investigational Site
Lebanon, New Hampshire, 03756
About this study
Official title: A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients
To characterize the effect of repeat oral dose of lapatinib treatment on the pharmacokinetics of a single oral and single intravenous dose of midazolam in adult cancer patients. Also to assess the safety and tolerability of chronic oral lapatinib therapy in cancer patients.
- Conditions
- Neoplasms, Breast
- Being tested
- Midazolam, Lapatinib
- Keywords
- midazolam, pharmacokinetics, lapatinib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Also called GW572016 oral tablets
Subjects will receive midazolam by oral or IV route on Days 1, 3, 9 and 11. Oral midazolam was supplied as 3 mg tablets; IV midazolam was supplied as 1 milligram per milliliter (mg/L) sterile solution.
LapatinibDrug
Subjects will receive 1500 mg lapatinib by oral route once daily from Day 4.
| Study group | Role | What they receive |
|---|---|---|
| Subjects with cancer | Experimental | In Part 1 of the study, subjects will be randomized to one of four sequences. All subjects will receive oral or intravenous (IV) midazolam on Days 1, 3, 9 and 11 as per assigned randomization scheme. Starting on Day 4 through Day 11, subjects will receive a daily dose of 1500 milligrams (mg) of oral lapatinib.
In Part 2, which will begin on Day 12, the subjects will be required to take 1500 mg of lapatinib daily until removed from the study for disease progression, adverse events, withdrawal of consent, or transfer to another lapatinib study. Receives: Drug: Midazolam; Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration versus time curve (AUC) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration. AUC of midazolam in the presence and absence of lapatinib will be determined.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Maximum observed concentration (Cmax) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration. Cmax of midazolam in the presence and absence of lapatinib will be determined.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Clearance (CL) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration. CL of midazolam in the presence and absence of lapatinib will be determined.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Half-life (t½) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration. t1/2 of midazolam in the presence and absence of lapatinib will be determined.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Absolute bioavailability (F) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration. Absolute bioavailability of midazolam in the presence and absence of lapatinib will be determined.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Secondary outcomes (7)
Time of maximum observed concentration (tmax) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Volume of distribution (Vss) of midazolam
Blood samples will be collected at indicated time points for the determination of midazolam concentration.
Measured: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events may require medical or surgical intervention to prevent one of the other outcomes listed above.
Measured: Up to Month 7
Number of subjects with abnormal clinical chemistry parameters
The following clinical chemistry parameters were evaluated: sodium, potassium, total carbon dioxide (CO2), calcium, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and blood urea nitrogen (BUN).
Measured: Up to Month 7
Number of subjects with abnormal hematology parameters
The following hematology parameters were evaluated: hemoglobin, hematocrit, red blood cell count, white blood cell count, neutrophil count, lymphocyte count, monocyte count, eosinophil count and basophil count.
Measured: Up to Month 7
Number of subjects with abnormal blood pressure
Systolic and diastolic blood pressure will be measured.
Measured: Up to Month 7
Number of subjects with abnormal heart rate
Heart rate will be measured.
Measured: Up to Month 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2005 (estimated)
- Study start21 Nov 2005
- Primary completion8 Feb 2007
- Study completion8 Feb 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00258050
- Sponsor's protocol ID
- EGF10015
- Status last verified
- Dec 2017
- First submitted
- 22 Nov 2005
- Last updated
- 6 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients
- ClinicalTrials.gov ID
- NCT00258050
- Acronym / sponsor ID
- EGF10015
- Conditions
- Neoplasms, Breast
- Keywords
- midazolam, pharmacokinetics, lapatinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2005 (actual)
- Primary completion
- 8 Feb 2007 (actual)
- Study completion
- 8 Feb 2007 (actual)
- First posted
- 24 Nov 2005 (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.
To characterize the effect of repeat oral dose of lapatinib treatment on the pharmacokinetics of a single oral and single intravenous dose of midazolam in adult cancer patients. Also to assess the safety and tolerability of chronic oral lapatinib therapy in cancer patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects with cancer | Experimental | Drug: Midazolam, Drug: LapatinibIn Part 1 of the study, subjects will be randomized to one of four sequences. All subjects will receive oral or intravenous (IV) midazolam on Days 1, 3, 9 and 11 as per assigned randomization scheme. Starting on Day 4 through Day 11, subjects will receive a daily dose of 1500 milligrams (mg) of oral lapatinib. In Part 2, which will begin on Day 12, the subjects will be required to take 1500 mg of lapatinib daily until removed from the study for disease progression, adverse events, withdrawal of consent, or transfer to another lapatinib study. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed, solid tumor refractory to standard therapy.
- Tumor for which there is no standard therapy.
- Able to swallow and retain oral medication.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
- Provided written informed consent.
Key exclusion criteria (17 listed)
- Pregnant or lactating female.
- Have malabsorption syndrome, a disease affecting gastrointestinal function.
- Resection of the stomach or small bowel.
- Evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease.
- Is considered medically unfit for the study by the investigator as a result of the medical interview, physical exam, or screening investigations.
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 |
|---|---|---|
| MidazolamAlso: GW572016 oral tabletsSubjects will receive midazolam by oral or IV route on Days 1, 3, 9 and 11. Oral midazolam was supplied as 3 mg tablets; IV midazolam was supplied as 1 milligram per milliliter (mg/L) sterile solution. | Drug | Subjects with cancer |
| LapatinibSubjects will receive 1500 mg lapatinib by oral route once daily from Day 4. | Drug | Subjects with cancer |
Primary outcome
Area under the concentration versus time curve (AUC) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. AUC of midazolam in the presence and absence of lapatinib will be determined.
Maximum observed concentration (Cmax) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. Cmax of midazolam in the presence and absence of lapatinib will be determined.
Clearance (CL) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. CL of midazolam in the presence and absence of lapatinib will be determined.
Half-life (t½) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. t1/2 of midazolam in the presence and absence of lapatinib will be determined.
Absolute bioavailability (F) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Blood samples will be collected at indicated time points for the determination of midazolam concentration. Absolute bioavailability of midazolam in the presence and absence of lapatinib will be determined.
7 secondary outcomes
Time of maximum observed concentration (tmax) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Volume of distribution (Vss) of midazolam
Time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11
Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to Month 7
Number of subjects with abnormal clinical chemistry parameters
Time frame: Up to Month 7
Number of subjects with abnormal hematology parameters
Time frame: Up to Month 7
Number of subjects with abnormal blood pressure
Time frame: Up to Month 7
Number of subjects with abnormal heart rate
Time frame: Up to Month 7
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 6 Dec 2017.
- Results for study EGF10015 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Midazolam and Lapatinib in people with Neoplasms, Breast, run by GlaxoSmithKline at 2 sites in United States.
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 12 inclusion and 17 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 6 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
Area under the concentration versus time curve (AUC) of midazolam (time frame: Pre-dose, 2 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours post-dose on Day 1, Day 3, Day 9 and Day 11). The study lists 5 primary outcomes in all. 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 6 Dec 2017.