Clinical trial NCT00732420: Open-label Study of Topotecan and Pazopanib in Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumours
Keywords: pazopanib
Phase I
topotecan
Advanced Solid Tumors
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-08-12
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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

Eligibility criteria: 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.

Primary outcomes:
measure: First course tolerability with rising dose of topotecan to determine the maximum tolerated dose of topotecan when given with pazopanib daily.
timeFrame: 5 weeks
Secondary outcomes:
measure: Indications of efficacy through tumour shrinkage. Specific biomarker analysis.
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: