Lapatinib and Vinorelbine in Treating Patients With Advanced Solid Tumors
NCT ID: NCT00389922
Last Updated: 2012-04-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
22 participants
INTERVENTIONAL
2005-12-31
2011-12-31
Brief Summary
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PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with vinorelbine in treating patients with advanced solid tumors.
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Detailed Description
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Primary
* Determine the safety and feasibility of 2 different schedules of lapatinib ditosylate when administered with vinorelbine ditartrate in patients with advanced solid tumors.
Secondary
* Determine the maximum tolerated dose (MTD) of each of these regimens in these patients.
* Determine, preliminarily, the efficacy of these regimens in these patients.
* Examine tissue and blood specimens from these patients to investigate potential predictors of response.
* Determine the pharmacokinetics of lapatinib ditosylate and vinorelbine ditartrate in patients treated at the MTD.
OUTLINE: This is a phase I study comprising 2 separate, sequential dose-escalation studies of lapatinib ditosylate. Patients are assigned to 1 of 2 treatment groups.
* Group A (daily dosing): Patients receive oral lapatinib ditosylate once daily on days 1-28 and vinorelbine ditartrate IV on days 1, 8, and 15.
Cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during course 1. At least 6 patients are treated at the MTD. Once the MTD of lapatinib has been determined, patients may be accrued to group B or to a separate pharmacokinetics cohort in group A.
* Pharmacokinetics (PK) cohort\*: Patients in the PK cohort receive vinorelbine ditartrate IV as in group A and oral lapatinib ditosylate once daily at the MTD on days 3-28 (course 1 only) and on days 1-28 in all subsequent courses. Patients undergo PK sampling during course 1.
NOTE: \*Accrual to group B and to the PK cohort of group A may occur simultaneously.
* Group B (intermittent dosing): Patients receive oral lapatinib ditosylate once daily at the MTD on days 2-5, 9-12, and 16-25 and vinorelbine ditartrate IV, on days 1, 8, and 15.
In both groups and in the PK cohort, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have completed 6 courses of combined therapy may receive additional courses with lapatinib ditosylate alone.
Patients undergo blood collection and buccal brushings periodically for pharmacokinetic and biomarker correlative studies. Archival tumor tissue is also evaluated for biomarkers, including epidermal growth factor receptor (EGFR) and HER-2/neu expression levels, EGFR polymorphisms and gene mutations (including RAS), levels of cellular proliferation and apoptosis, and RAS mutations by immunohistochemistry, mutation analysis, TUNEL assay, and polymerase chain reaction.
After completion of study treatment, patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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A (Daily Dosing)
Oral lapatinib given daily for 28 days plus IV vinorelbine given weekly (3 out of 4 weeks)
Cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during course 1. At least 6 patients are treated at the MTD. Once the MTD of lapatinib has been determined, patients may be accrued to group B or to a separate pharmacokinetics cohort in group A.
lapatinib ditosylate
Given orally for 28 days per dose level (Dose level 1: 250mg; Dose level 2: 500mg; Dose level 3: 1000mg; Dose level 4: 1250mg; Dose level 5: 1500mg; Dose level 6: 1500mg)
vinorelbine ditartrate
Given IV Days 1, 8 and 15 per dose level (Dose level 1: 20mg/m2; Dose level 2: 20mg/m2; Dose level 3: 20mg/m2; Dose level 4: 20mg/m2; Dose level 5: 20mg/m2; Dose level 6: 25mg/m2)
comparative genomic hybridization
Molecular correlative study
cytogenetic analysis
Molecular correlative study
gene expression analysis
Molecular correlative study
mutation analysis
Molecular correlative study
polymerase chain reaction
Molecular correlative study
polymorphism analysis
Molecular correlative study
proteomic profiling
Molecular correlative study
reverse transcriptase-polymerase chain reaction
Molecular correlative study
immunohistochemistry staining method
Molecular correlative study
laboratory biomarker analysis
Molecular correlative study
B (Intermittent Dosing)
Oral lapatinib given days 2-5, 9-12 and 16-25 plus IV vinorelbine given weekly (3 out of 4 weeks)
Cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during course 1. At least 6 patients are treated at the MTD. Once the MTD of lapatinib has been determined, patients may be accrued to group B or to a separate pharmacokinetics cohort in group A.
lapatinib ditosylate
Given orally on Days 2-5, 9-12 and 16-25 per dose level (Dose level 1: 1250mg; Dose level 2: 1500mg; Dose level 3: 1500mg; Dose level 4: 1700mg)
Vinorelbine ditartrate
Given IV Days 1, 8 and 15 per dose level (Dose level 1: 20mg/m2; Dose level 2: 20mg/m2; Dose level 3: 25mg/m2; Dose level 4: 25mg/m2)
Interventions
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lapatinib ditosylate
Given orally for 28 days per dose level (Dose level 1: 250mg; Dose level 2: 500mg; Dose level 3: 1000mg; Dose level 4: 1250mg; Dose level 5: 1500mg; Dose level 6: 1500mg)
vinorelbine ditartrate
Given IV Days 1, 8 and 15 per dose level (Dose level 1: 20mg/m2; Dose level 2: 20mg/m2; Dose level 3: 20mg/m2; Dose level 4: 20mg/m2; Dose level 5: 20mg/m2; Dose level 6: 25mg/m2)
comparative genomic hybridization
Molecular correlative study
cytogenetic analysis
Molecular correlative study
gene expression analysis
Molecular correlative study
mutation analysis
Molecular correlative study
polymerase chain reaction
Molecular correlative study
polymorphism analysis
Molecular correlative study
proteomic profiling
Molecular correlative study
reverse transcriptase-polymerase chain reaction
Molecular correlative study
immunohistochemistry staining method
Molecular correlative study
laboratory biomarker analysis
Molecular correlative study
lapatinib ditosylate
Given orally on Days 2-5, 9-12 and 16-25 per dose level (Dose level 1: 1250mg; Dose level 2: 1500mg; Dose level 3: 1500mg; Dose level 4: 1700mg)
Vinorelbine ditartrate
Given IV Days 1, 8 and 15 per dose level (Dose level 1: 20mg/m2; Dose level 2: 20mg/m2; Dose level 3: 25mg/m2; Dose level 4: 25mg/m2)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Measurable or evaluable disease. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy.
* 18 years of age or older.
* Zubrod performance status of 0-2.
* Estimated survival of at least 3 months.
* Any prior chemotherapy must have been completed at least 4 weeks prior to start of this protocol and all side effects (except alopecia) resolved to grade 1 or less. Any prior radiation must have been completed at least 2 weeks prior to start of therapy. For prior mitomycin chemotherapy a 6-week interval is required. Patients must have completed prior trastuzumab at least 4 weeks prior to start of protocol therapy.
* Adequate renal function
* Adequate liver function
* Pretreatment granulocyte count of \>1500/mm3 and platelet count of \>100 000/mm3.
* Cardiac ejection fraction within the institutional range of normal as measured by 2-D echocardiogram or MUGA scan.
* Asymptomatic treated brain metastasis may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 4 weeks.
* All patients must give informed consent.
* Able to take and retain oral medication.
* Patients of reproductive potential must agree to use an effective contraceptive method
Exclusion Criteria
* Females cannot be pregnant or breastfeeding
* Symptomatic brain metastasis or still requiring steroids and anticonvulsants may not participate.
* Pre-existing neuropathy \> grade 2 may not participate.
* 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, will be excluded.
* History of other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications.
* Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption.
* HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib.
* Patients requiring oral anticoagulants are eligible provided there is appropriate close INR monitoring is in place. If medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with lapatinib is not expected.
* Adherence to the requirements for concomitant medications classified as CYP3A4 inducers or inhibitors, or gastric pH modifiers
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
University of California, Davis
OTHER
Responsible Party
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Principal Investigators
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Helen K. Chew, MD
Role: STUDY_CHAIR
University of California, Davis
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States
University of California Davis Cancer Center
Sacramento, California, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
Countries
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Other Identifiers
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UCDCC-171
Identifier Type: OTHER
Identifier Source: secondary_id
UCDCC-200513681-1
Identifier Type: OTHER
Identifier Source: secondary_id
GSK-104241
Identifier Type: OTHER
Identifier Source: secondary_id
CDR0000505878
Identifier Type: -
Identifier Source: org_study_id
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