Last updated: 11/04/2018 13:09:38
Study Of Safety And Tolerability Of GW786034 Given With Lapatinib In Cancer Patients
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: An Open-Label, Safety, Pharmacokinetic and Pharmacodynamic Study of Multiple Doses of GW786034 and Lapatinib Concomitantly Administered in Cancer Patients
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Changes in pre and post treatment lab values and monitoring/reporting AES.AE's throughout study
Timeframe: throughout study
Labs every wk first cycle:day 1 subsequent cycles
Timeframe: first cycle:day 1 subsequent cycles
Secondary outcomes:
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
Timeframe: Blood taken day 15, 22 or 37 and tumor assessed every 8 wks
Interventions:
Drug: GW786034
Drug: lapatinib
Enrollment:
75
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
deJonge MJA, Hamberg P, Verweij J, et al. Phase I and Pharmacokinetic Study of Pazopanib and Lapatinib Combination Therapy in Patients with Advanced Solid Tumors. Invest New Drugs. 2013;31(3):751-759.
Medical condition
Carcinoma, Renal Cell
Product
lapatinib, pazopanib
Collaborators
Not applicable
Study date(s)
September 2004 to August 2007
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
21+ years
Accepts healthy volunteers
No
- 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:
- Had prior treatment with either study drug.
- Has brain metastases.
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
- ANC greater than or equal to 1,500/mm3 (1.5 x 109/L).
- Hgb greater than or equal to 9 g/dL (5 mmol/L).
- CLcr > 50 mL/min as calculated by the Cockcroft-Gault formula.
- Total bilirubin less than or equal to 1.5 x upper limit of normal.
- PT/INR/PTT less than or equal to 1.2 x upper limit of normal.
- AST/ALT less than or equal to 3 x upper limit of normal.
- Has LVEF within normal range or above 50% based on MUGA/ECHO.
- Urinalysis for protein is < 2 (negative, trace, or 1). NOTE: If urinalysis is 2 or greater then a 24 hour urine for protein must demonstrate less than 1 gram of protein in 24 hours for patient to be eligible for enrollment.
- Able to swallow and retain oral medication.
- Has a life expectancy of at least 12 weeks.
Exclusion criteria:
- 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.
Trial location(s)
Location
GSK Investigational Site
Durham, North Carolina, United States, 27705
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2007-21-08
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study VEG10006 can be found on the GSK Clinical Study Register.
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