Study Of Safety And Tolerability Of GW786034 Given With Lapatinib In Cancer Patients

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00158782
First received: September 8, 2005
Last updated: March 17, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Carcinoma, Renal Cell
Cancer
Drug: GW786034
Drug: lapatinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Safety, Pharmacokinetic and Pharmacodynamic Study of Multiple Doses of GW786034 and Lapatinib Concomitantly Administered in Cancer Patients.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Changes in pre and post treatment lab values and monitoring/reporting AES.AE's throughout study [ Time Frame: throughout study ]
  • Labs every wk first cycle:day 1 subsequent cycles [ Time Frame: first cycle:day 1 subsequent cycles ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Blood taken day 15, 22 or 37 and tumor assessed every 8 wks ]

Estimated Enrollment: 65
Study Start Date: September 2004
Intervention Details:
    Drug: GW786034 Drug: lapatinib
    Other Names:
    • GW786034
    • lapatinib
  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00158782

Locations
United States, North Carolina
GSK Investigational Site
Durham, North Carolina, United States, 27705
Netherlands
GSK Investigational Site
Rotterdam, Netherlands, 3075 EA
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00158782     History of Changes
Other Study ID Numbers: VEG10006
Study First Received: September 8, 2005
Last Updated: March 17, 2011
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Cancer GW786034 Lapatinib Pazopanib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Lapatinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014