Phase II, open-label, non-randomized, international multicenter clinical trial with two strata (SFT and EMC). 8 sites in Spain, 5 sites in Italy and 5 sites in France. Patients will receive oral pazopanib at 800 mg once daily continuously. Patients will continue to receive treatment until there is evidence of progressive disease, unacceptable toxicity, non-compliance, withdrawn consent or investigator decision. The main goal is to determine the objective response rate (ORR) (confirmed complete response \[CR\] and partial response \[PR\]) in patients with unresectable, locally advanced or metastatic solitary fibrous tumor and extraskeletal myxoid chondrosarcoma, using Choi and RECIST 1.1 criteria respectively.
To estimate the sample size for stratum 1 (SFT), a Simon's optimal 2-stage phase II design has been used, having considered the published response rate based on Choi criteria in SFT patients which correspond to 40% in monotherapy. For a design with P0=0.40, P1=0.60; α=0.1 and β=0.1. At the first stage, 18 patients should be enrolled into the study, if there are fewer than 8 responses (7 or less) the trial will be terminated and it will be concluded that pazopanib is not sufficiently active. At the second stage, another 28 patients (total 46 patients) would be enrolled into the study. To reject the null hypothesis for the SFT stratum 23 responses or more (Choi criteria), out of the 46 patients, are needed. To estimate the simple size for stratum 2 (EMC), a Simon's optimal 2-stage phase II design has been used, having considered the very scarce published information on response rate based on RECIST criteria. For a design with P0= 0.05, P1= 0.25, α=0.1 and β=0.1. At the first stage, 9 patients should be enrolled into the study, if there are not responses the trial will be terminated and it will be concluded that pazopanib is not sufficiently active. If there is at least 1 response in this first stage, the trial will be continued and at the second stage, another 15 patients (total 24 patients) would be enrolled into the study. To reject the null hypothesis for the EMC stratum 3 responses or more (RECIST criteria), out of the 24 patients, are needed. For variables that follow binomial distributions (e.g. response rate) frequency and percentages will be calculated, together with their corresponding exact 95% confidence intervals. For time-to-event variables (e.g. PFS or OS) Kaplan-Meier estimations will be used. To analyze the reduction of risk and the influence of other variables on time-to-event variables Cox Regression will be applied. To correlate pharmacodynamics markers and biomarkers with clinical response standard methods for bivariate and multivariate regression and correlation will be used.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
96
Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.
H. Son Espases
Palma de Mallorca, Balearic Islands, Spain
H. Universitario de Canarias
Santa Cruz de Tenerife, Santa Cruz De Tenerife, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital La Paz
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Universitario Virgen del Rocío
Seville, Spain
H. Miguel Servet
Zaragoza, Spain
Objective response rate (ORR)
Objective response rate (ORR) (confirmed complete response \[CR\] and partial response \[PR\]), measured using Choi and RECIST 1.1 criteria. Response criteria will be based on the baseline identification of target lesions and follow-up until tumor progression.
Time frame: 48 weeks
Efficacy of pazopanib
Efficacy measured by the progression-free survival (PFS) rate assessed by median time
Time frame: 48 weeks
Overall survival (OS)
Overall survival (OS) measured since treatment start date until date of death, whichever the cause
Time frame: 72 weeks
Clinical benefit rate (CBR)
Clinical benefit rate (CBR). Patients who have reached CR, PR or SD during 6 months or more, presenting clinical improvement of symptoms, will be considered as having experienced clinical benefit.
Time frame: 48 weeks
Long term safety profile of pazopanib
Long term safety profile of pazopanib, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using NCI-CTCAE 4.0.
Time frame: 48 weeks
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