The purpose of this clinical research study is to learn if pazopanib when given in combination with topotecan can help to control sarcomas. The safety of this drug combination will also be studied. Pazopanib hydrochloride and topotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine progression free rate at week 12 for patients with soft tissue sarcoma (STS) treated with pazopanib (pazopanib hydrochloride) plus oral topotecan (topotecan hydrochloride). SECONDARY OBJECTIVES: I. To determine the overall response rate for patients with STS treated with combination pazopanib and topotecan. II. To determine the clinical benefit rate (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]) for patients with STS treated with combination pazopanib and topotecan. III. To determine median progression-free rate (PFR) for patients with STS treated with combination pazopanib and topotecan. IV. To evaluate overall survival (OS) for patients with STS treated with combination pazopanib and topotecan. V. To assess safety and tolerability for patients treated with combination pazopanib and topotecan. VI. To estimate the PFR for patients with osteosarcoma treated with combination pazopanib and topotecan. VII. To estimate the PFR for patients with liposarcoma treated with combination pazopanib and topotecan. TERTIARY OBJECTIVES: I. To estimate the correlation of PFR and OS to levels of soluble vascular endothelial growth factor receptor 2 (sVEGFR2) and phosphatidylinositol-glycan biosynthesis class F (PIGF). OUTLINE: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 and topotecan hydrochloride PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity or until discontinuation per patient preference or physician recommendation. After completion of study treatment, patients are followed up every 6 months for 2 or 5 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
178
Given PO
Given PO
Correlative studies
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Mayo Clinic in Florida
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Northwestern University- Lake Forest Hospital
Lake Forest, Illinois, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Progression Free Survival at 12 Weeks for Patients With Soft Tissue Sarcoma (STS) Treated With Pazopanib and Oral Topotecan
PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1 and measured at 12 weeks after treatment initiation for patients with STS. PFS estimates will be calculated using Kaplan-Meier methods Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.
Time frame: At 12 weeks from treatment initiation
Overall Response Rate (ORR) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.
ORR is defined as the percentage of patients with Complete Response (CR) plus those with Partial Response (PR) as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients best response to treatment will be used in ORR. Complete Response - Disappearance of all target and non target lesions Partial Response - At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
Time frame: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33.
Clinical Benefit Rate (CBR) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.
CBR is defined as the percentage of patients with Complete Response (CR) plus those with Partial Response (PR) plus those with Stable Disease (SD) as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients best response to treatment will be used in CBR where, in general the following definitions are used: Complete Response - Disappearance of all target and non target lesions Partial Response - At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started.
Time frame: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33.
Overall Survival (OS) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.
OS will be defined from start of study until death from any cause and estimates will be calculated using Kaplan-Meier methods. At time of Kaplan-meier calculations patients included the analysis who have not experienced the event will be censored at the last date of documentation of survival status.
Time frame: During treatment where one cycle = 28 days and range of cycles completed by patients 1-33, then for 2 years (for patients with progression) and 5 years (for patients without progression) following discontinuation of treatment
Number of Patients With Significant Adverse Events, Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
Toxicities will be tabulated and summarized by the number of patients experiencing each toxicity at grade 3 or grade 4
Time frame: From treatment initiation until 30 days post last treatment, at the beginning of each cycle where 1 cycle=28 days. Range of cycles completed by patients 1-33 cycles
Median Progression Free Survival (PFS) for Patients With Soft Tissue Sarcoma (STS) Treated With Combination Pazopanib and Topotecan.
PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1. PFS estimates will be calculated using Kaplan-Meier methods. Patients included in the analysis, who did not experiences the event at the time of the calculation were censored from the last documentation of being progression free. Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.
Time frame: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. And then for up to 5 years post treatment discontinuation.
Progression Free Survival in Patients With Osteosarcoma Treated With Combination Pazopanib and Topotecan.
PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1. PFS estimates will be calculated using Kaplan-Meier methods. Patients included in the analysis, who did not experiences the event at the time of the calculation were censored from the last documentation of being progression free. Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.
Time frame: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. Then for up to 5 years post treatment discontinuation
Progression Free Survival for Patients With Liposarcoma Treated With Combination Pazopanib and Topotecan.
PFS will be defined from the time of enrollment to the study until progression of disease or death from any cause, as assessed by RECIST 1.1. PFS estimates will be calculated using Kaplan-Meier methods. Patients who did not experiences the event at the time of the calculation were censored from the last documentation of being progression free. Progression is defined as at least a 20% increase in the sum of the Longest Diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Progression must also involve an increase in size of measurable lesions by at least 5 mm, to minimize the possibility that small changes in a small number of target lesions is falsely interpreted as progression.
Time frame: During treatment, assessed at 6 weeks, 12 weeks, 20 weeks and then every 2 cycles where one cycle = 28 days and range of cycles completed by patients 1-33. Then up to 5 years post treatment discontinuation.
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