Open-label Study of Topotecan and Pazopanib in Advanced Solid Tumors

Study Overview
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Brief Summary
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To determined what dose of topotecan can be safely given with daily pazopanib.

Detailed Description
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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

Official Title
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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

Conditions
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Solid Tumours

Intervention / Treatment
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* Drug: topotecan
* Drug: pazopanib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A<br>Daily oral pazopanib in combination with weekly oral topotecan. Initially rising dose to determine the maximum tolerated dose: finally an expanded cohort treated at the maximum tolerated dose. | Drug: topotecan<br>* Topoisomerase I inhibition.<br>Drug: pazopanib<br>* Tyrosine kinase inhibitor<br>|
| Experimental: Treatment Arm B<br>Daily oral pazopanib in combination with oral topotecan given for 5 consecutive days every 21 days. Initially rising dose to determine the maximum tolerated dose; finally an additional cohort of patients treated at the maximum tolerated dose. | Drug: topotecan<br>* Topoisomerase I inhibition.<br>Drug: pazopanib<br>* Tyrosine kinase inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Indications of efficacy through tumour shrinkage. Specific biomarker analysis. |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pazopanib, Phase I, topotecan, Advanced Solid Tumors