Study Of Safety And Tolerability Of GW786034 Given With Lapatinib In Cancer Patients
An Open-Label, Safety, Pharmacokinetic and Pharmacodynamic Study of Multiple Doses of GW786034 and Lapatinib Concomitantly Administered in Cancer Patients
1 other identifier
interventional
75
2 countries
2
Brief Summary
This Phase I, dose finding study evaluates the safety and tolerability of lapatinib, a dual tyrosine kinase inhibitor, and GW786034, an anti-angiogenesis agent, when given together. The study first will find the best doses using safety and blood concentration data of both agents. This is done enrolling stepwise, cohorts of 3 patients each and the last patient enrolled must reach at least Day 22 of continuous daily dosing before the next cohort at an increased dose can begin. If a patient in a cohort has a dose limiting toxicity before Day 22, then 3 more patients are studied at that same dose. If 2 of 6 patients have dose limiting toxicities within the first 22 days, the next cohort receives the next lowest dose. Otherwise each cohort has an increasing dose of one of the two agents. The second stage of the study will administer the best doses of the agents to about 16 patients to further study safety and collect more blood concentration data (more blood samples in the second phase compared to the first phase). The second stage has the advantage of using the best dose (decreases chance of receiving a sub-therapeutic dose) while it collects more blood samples and requires slightly more long clinic visits.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2004
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 28, 2004
CompletedFirst Submitted
Initial submission to the registry
September 8, 2005
CompletedFirst Posted
Study publicly available on registry
September 12, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 21, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
August 21, 2007
CompletedNovember 17, 2017
November 1, 2017
2.9 years
September 8, 2005
November 13, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Changes in pre and post treatment lab values and monitoring/reporting AES.AE's throughout study
throughout study
Labs every wk first cycle:day 1 subsequent cycles
first cycle:day 1 subsequent cycles
Secondary Outcomes (1)
find max conc of drugs in blood and time it occurs find out if drugs are taken up by the body, how much/for how long find out if drugs affect the size of the tumor. Blood taken day 15, 22 or 37 and tumor assessed every 8 wks
Blood taken day 15, 22 or 37 and tumor assessed every 8 wks
Study Arms (10)
Cohort 1
EXPERIMENTALSubjects will receive GW786034 500 milligrams and lapatinib 750 milligrams.
Cohort 2
EXPERIMENTALSubjects will receive GW786034 250 milligrams and lapatinib 750 milligrams.
Cohort 3
EXPERIMENTALSubjects will receive GW786034 250 milligrams and lapatinib 1000 milligrams.
Cohort 4
EXPERIMENTALSubjects will receive GW786034 500 milligrams and lapatinib 1000 milligrams.
Cohort 5
EXPERIMENTALSubjects will receive GW786034 250 milligrams and lapatinib 1250 milligrams.
Cohort 6
EXPERIMENTALSubjects will receive GW786034 400 milligrams and lapatinib 1250 milligrams.
Cohort 7
EXPERIMENTALSubjects will receive GW786034 200 milligrams and lapatinib 1500 milligrams.
Cohort 8
EXPERIMENTALSubjects will receive GW786034 400 milligrams and lapatinib 1500 milligrams.
Cohort 9
EXPERIMENTALSubjects will receive GW786034 400 milligrams and lapatinib 1000 milligrams.
Cohort 10
EXPERIMENTALSubjects will receive GW786034 800 milligrams and lapatinib 1500 milligrams.
Interventions
GW786034 (Pazopanib) is an orally active, potent, reversible, small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, VEGFR-3, platelet-derived growth factor receptor-alpha (PDGFR-alpha), PDGFR-beta, and c-Kit.
Lapatinib is an oral, reversible, tyrosine kinase inhibitor of both epidermal growth factor receptor-1 (ErbB1) and ErbB2.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed diagnosis of advanced solid tumor refractory to standard therapy or for whom there is no standard therapy.
- Females are eligible if they are of:
- a) Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:
- had a hysterectomy.
- had a bilateral oophorectomy (ovariectomy).
- had a bilateral tubal ligation.
- is post-menopausal (a demonstration of total cessation of menses for 1 year).
- childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following:
- an IUD with a documented failure rate of less than 1% per year.
- vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female.
- complete abstinence from sexual intercourse for 14 days before exposure to investigational product, throughout the clinical trial, and for at least 14 days after the last dose of investigational product.
- double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).
- ECOG (Eastern Cooperative Oncology Group) PS 0 or 1.
- Adequate bone marrow function.
- Platelets greater than or equal to 75,000/mm3.
- +10 more criteria
You may not qualify if:
- Had prior treatment with either study drug.
- Has brain metastases.
- Uncontrolled hypertension (BP higher than 150/90 SBP/DBP).
- Have heart failure.
- Have DVT (deep vein thrombosis) or arterial thrombosis, MI (myocardial infarction), angina, or has had angioplasty and/or stenting within last 3 months.
- Has allergy to drug similar to lapatinib (e.g. allergic to Iressa(gefitinib) or Tarceva(erlotinib).
- Is using therapeutic doses of anti-coagulant.
- Has had major surgery, hormonal therapy, chemotherapy, radiotherapy, or other investigational agent within last 28 days.
- Pregnant or lactating.
- History or current GI (gastrointestinal) condition that alters stomach or gut emptying from normal (e.g. major surgery on the stomach).
- Bowel obstruction or chronic diarrhea.
- Psychological or geographical conditions that would prevent him/her from being a good candidate.
- Do not have accessible veins for venipuncture.
- History of prolonged QTc on ECG.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (2)
GSK Investigational Site
Durham, North Carolina, 27705, United States
GSK Investigational Site
Rotterdam, 3075 EA, Netherlands
Related Publications (1)
de Jonge MJ, Hamberg P, Verweij J, Savage S, Suttle AB, Hodge J, Arumugham T, Pandite LN, Hurwitz HI. Phase I and pharmacokinetic study of pazopanib and lapatinib combination therapy in patients with advanced solid tumors. Invest New Drugs. 2013 Jun;31(3):751-9. doi: 10.1007/s10637-012-9885-8. Epub 2012 Oct 6.
PMID: 23054212BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 8, 2005
First Posted
September 12, 2005
Study Start
September 28, 2004
Primary Completion
August 21, 2007
Study Completion
August 21, 2007
Last Updated
November 17, 2017
Record last verified: 2017-11