Solid Tumours
Conditions
Keywords
pazopanib, Phase I, topotecan, Advanced Solid Tumors
Brief summary
To determined what dose of topotecan can be safely given with daily pazopanib.
Detailed description
A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of Two Schedules of Oral Topotecan in combination with Pazopanib in Subjects with Advanced Solid Tumors
Interventions
DRUGtopotecan
Topoisomerase I inhibition.
DRUGpazopanib
Tyrosine kinase inhibitor
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- * signed, written informed consent. * at least 18 years of age. * ECOG performance status 0 or 1. * Subjects must have histologically or cytologically confirmed diagnosis of advanced cancer and a solid tumor malignancy that has relapsed or is refractory to standard therapy or for which there is no established therapy. * able to swallow and retain oral medications. * females are eligible to enter and participate in this study providing adequate established contraception is being practiced.
Exclusion criteria
* had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) * received an investigational drug within 30 days or 5 half-lives (whichever is longer). * received prior treatment with pazopanib/investigational anti-angiogenic compounds. * presence of uncontrolled infection. * pregnant or lactating. * poorly controlled hypertension (SBP of ? 140 mmHg, or DBP of ? 90 mmHg. * Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.- * arterial thrombi, myocardial infarction, admission for unstable angina, uncontrolled or symptomatic arrhythmia, cardiac angioplasty, or stenting within the last 6 months. * any unresolved bowel obstruction or diarrhea ? Grade 1. * received an allogeneic bone marrow transplant. * known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or topotecan. * any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance with the study. * psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. * clinical history, current alcohol or illicit drug use which, in the judgment of the investigator, would interfere with the subject's ability to comply with the dosing schedule and protocol-specified evaluations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| First course tolerability with rising dose of topotecan to determine the maximum tolerated dose of topotecan when given with pazopanib daily. | 5 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Indications of efficacy through tumour shrinkage. Specific biomarker analysis. | 12 weeks |
Countries
Netherlands, United States
Outcome results
None listed