Pazopanib monotherapy is approved by the Food and Drug Administration (FDA), European Medicines Agency, and other regulatory authorities worldwide for the treatment of patients with advanced renal cell carcinoma and patients with advanced soft tissue sarcoma (STS) who received prior chemotherapy. Based on the improved progression-free survival and sustained responses observed in a pivotal Phase 3, randomized, placebo-controlled study, it is hypothesized that pazopanib may have a role in a maintenance setting for STS in maintaining the initial response to chemotherapy and delaying the need for further treatment at relapse and its associated toxicity and impact on health-related quality-of-life. This Phase 2, randomized, double-blind, placebo-controlled study will evaluate maintenance therapy with pazopanib versus placebo in subjects with advanced or metastatic STS who have not progressed after 4 to 6 cycles of first-line anthracycline-based chemotherapy. Approximately 188 eligible subjects will be randomized in a 1:1 ratio to treatment with pazopanib 800 milligrams (mg) daily or placebo. Study completion will be the point at which 70% of randomized subjects have died. Once a subject has objective evidence of disease progression, the subject will be managed as per standard practice by their physician. Subjects will continue to be followed for second progression, health related quality of life, survival until study completion, withdrawal of consent, or early termination of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Aqueous film-coated, oval-shaped, white tablets containing either 200 mg or 400 mg pazopanib
Tablets matching the 200 mg and 400 mg pazopanib tablets
Progression-free survival (PFS)
PFS is defined as time from randomization to development of disease progression or death due to any cause. Disease progression will be evaluated based on investigators' radiologic assessments by Response Evaluation Criteria in Solid Tumors \[RECIST\] version 1.1
Time frame: At Day 57 and every 8 weeks thereafter until disease progression or death (assessed up to 2 years)
Overall survival (OS)
OS is defined as time from randomization to death due to any cause.
Time frame: At Day 57, then every 8 weeks until disease progression, and every 3 months thereafter until death (assessed up to 2 years)
Disease control rate (DCR)
DCR is defined as percentage of complete response + partial response + stable disease at 4 months after randomization based on RECIST version 1.1.
Time frame: At 4 months after randomization
Safety and tolerability as assessed by physical examination findings
A brief physical examination will include height (baseline only), body weight and evaluation of the subject's medical conditions
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Safety and tolerability as assessed by temperature measurement
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Safety and tolerability as assessed by systolic and diastolic blood pressure measurement
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Safety and tolerability as assessed by pulse rate measurement
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Safety and tolerability as assessed by composite of clinical laboratory tests
Clinical laboratory tests will include chemistry and hematology parameters
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Safety and tolerability as assessed by cardiac assessments
Cardiac assessments will include twelve-lead electrocardiogram (ECG), echocardiogram (ECHO) or multigated angiogram (MUGA) assessments
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Safety and tolerability as assessed by number of subjects with adverse event
Time frame: From Day 1 up to end of treatment (assessed up to 2 years)
Time to worsening of dyspnea or pain scores as measured by the MD Anderson Symptom Inventory (MDASI) questionnaire
The MDASI is a 19-item general cancer questionnaire asking subjects to rate symptoms at their worst on a scale of 0-10, including pain and shortness of breath as items. Time to symptom deterioration is defined as worsening in tumour pain score or dyspnea score of 2 points or more from baseline, confirmed by at least one additional weekly measure within a four week period.
Time frame: Weekly from baseline up to week 48
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