Sarcoma, Soft Tissue
Conditions
Keywords
Soft tissue sarcoma, Pazopanib, Tyrosine kinase inhibitor
Brief summary
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.
Interventions
DRUGPazopanib 800 mg
Aqueous film-coated, oval-shaped, white tablets containing either 200 mg or 400 mg pazopanib
DRUGPlacebo
Tablets matching the 200 mg and 400 mg pazopanib tablets
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide signed written informed consent before performing study-specific procedures or assessments and are willing to comply with treatment and follow-up. * Age \>= 18 years * Have a local histopathological diagnosis of one the following STS tumor types based on World Health Organization (WHO) 2013 classification. Fibroblastic (adult fibrosarcoma, myxofibrosarcoma, sclerosing epithelioid fibrosarcoma, malignant solitary fibrous tumors), Leiomyosarcoma , Vascular (epithelioid haemangioendothelioma, angiosarcoma), Skeletal muscle (pleomorphic and alveolar rhabdomyosarcoma only), Malignant peripheral nerve sheath tumors, Malignant glomus tumors, Alveolar soft part sarcoma, Uncertain differentiation (synovial, epithelioid, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor \[PEComa\], intimal sarcoma), Undifferentiated soft tissue sarcomas (undifferentiated pleomorphic sarcoma or undifferentiated not otherwise specified), Other types of sarcoma not in listed
Exclusion criteria
(contact medical monitor in case of unclear eligibility of a given subtype) * Completed 4 to 6 cycles of first-line anthracycline-based chemotherapy for metastatic disease without disease progression. Note: Subjects must have no evidence of radiological progression as confirmed by Computed Tomography (CT)/ Magnetic Resonance Imaging (MRI) within 4 weeks before randomization and no signs of clinical progression before randomization. * The date of study randomization must be 3 to 8 weeks following the last dose of chemotherapy. All chemotherapy-related side effects (except alopecia) must have resolved to grade 1 or better. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Able to swallow and retain oral tablets. * Adequate baseline organ function * Baseline Left Ventricular Ejection Fraction (LVEF) above lower limit of normal (LLN) based on institution's normal range. * Corrected QT interval (QTc) \<450 milliseconds (msec) or QTc \<480 msec for subjects with bundle branch block. For subject eligibility and withdrawal, Bazett's QT correction formula (QTcB) will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period. * Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study treatment and agree to use effective contraception, as defined in Study Protocol during the study and for 14 days following the last dose of study treatment. Note: Female subjects who are lactating must discontinue nursing before the first dose of study treatment and refrain from nursing from the first dose until 14 days following the last dose of study treatment. * French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | At Day 57 and every 8 weeks thereafter until disease progression or death (assessed up to 2 years) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | At 4 months after randomization | DCR is defined as percentage of complete response + partial response + stable disease at 4 months after randomization based on RECIST version 1.1. |
| Safety and tolerability as assessed by physical examination findings | From Day 1 up to end of treatment (assessed up to 2 years) | A brief physical examination will include height (baseline only), body weight and evaluation of the subject's medical conditions |
| Safety and tolerability as assessed by temperature measurement | 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 | From Day 1 up to end of treatment (assessed up to 2 years) | — |
| Overall survival (OS) | At Day 57, then every 8 weeks until disease progression, and every 3 months thereafter until death (assessed up to 2 years) | OS is defined as time from randomization to death due to any cause. |
| Safety and tolerability as assessed by composite of clinical laboratory tests | From Day 1 up to end of treatment (assessed up to 2 years) | Clinical laboratory tests will include chemistry and hematology parameters |
| Safety and tolerability as assessed by cardiac assessments | From Day 1 up to end of treatment (assessed up to 2 years) | Cardiac assessments will include twelve-lead electrocardiogram (ECG), echocardiogram (ECHO) or multigated angiogram (MUGA) assessments |
| Safety and tolerability as assessed by number of subjects with adverse event | 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 | Weekly from baseline up to week 48 | 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. |
| Safety and tolerability as assessed by pulse rate measurement | From Day 1 up to end of treatment (assessed up to 2 years) | — |
Outcome results
None listed