Clinical trial NCT01506596: Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma
Official title: A Phase II Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liposarcoma
Surgically Unresectable Liposarcoma
Metastatic Liposarcoma
Keywords: Liposarcoma
Lead sponsor: Vector Oncology
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2012-01-10
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness and safety of single agent pazopanib in subjects with unresectable or metastatic liposarcoma.

Detailed description: This is a Phase II, multicenter, prospective, open label, single arm study. The primary endpoint of the study is progression-free rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 at week 12 after start of treatment. The secondary endpoints include overall progression-free survival (PFS), response rate (RR), duration of response, overall survival (OS), and toxicity assessment through the reporting of adverse events.

Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Age \> or = to 18 years.
* Histologically or cytologically confirmed high- or intermediate-grade liposarcoma (allowed subtypes include liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, or not otherwise specified).
* Surgically unresectable or metastatic disease.
* Any number of prior treatment treatment regimens, including treatment naive subjects.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Measurable or evaluable (non-measurable) disease per RECIST guidelines version 1.1. Subjects must have documented disease progression within the past 6 months.
* Adequate organ system function determined within 14 days prior to first dose of study treatment.
* Left ventricular ejection fraction (LVEF) \> 50% of the institutional LLN within 28 days prior to the first dose of study treatment.
* Females must be of either non-child bearing potential or have a negative pregnancy test within 7 days prior to the first dose of study treatment.

Exclusion Criteria:

* Well differentiated liposarcoma.
* Prior treatment with tyrosine kinase inhibitors (TKIs) or vascular endothelial growth factor (VEGF) inhibitors.
* Prior malignancy (Note: subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible).
* History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, unless previously treated, asymptomatic, and off steroids and anti-seizure medication for 6 months prior to first dose of study drug
* Clinically significant gastrointestinal (GI) abnormalities that may increase the risk for GI bleeding.
* Clinically significant GI abnormalities that may affect absorption of investigational product.
* Presence of uncontrolled infection.
* Corrected QT interval \> 480 msecs using Bazett's formula.
* History of certain cardiovascular conditions within the past 6 months.
* Poorly controlled hypertension \[defined as systolic blood pressure of \> or = 140 mmHg or diastolic blood pressure \> or = 90 mmHg\].
* History of cerebrovascular accident including transient ischemic attack, pulmonary embolism, or untreated deep vein thrombosis within the past 6 months.
* Prior major surgery or trauma within 28 days prior to the first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
* Evidence of active bleeding or bleeding diathesis.
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.
* Hemoptysis in excess of 2.5 mL within 8 weeks of first dose of study drug.
* Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
* Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug, whichever is longer, prior to the first dose of study drug and for the duration of study treatment.
* Radiation therapy, minor surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug.
* Administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to receiving the first dose of study drug.
* Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 and/or that is progressing in severity, except alopecia.
* Known immediate or delayed hypersensitivity reaction to idiosyncrasy to drugs chemically realted to pazopanib or excipients that contraindicates participation.

Primary outcomes:
measure: 12-week Progression Free Rate
timeFrame: Assessed after 12 weeks of study treatment
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Date of Consent until progression or death, up to 27 months
measure: Best Overall Response
timeFrame: Date of consent until end of study treatment, up to 32 months
measure: Duration of Response
timeFrame: Measure of the amount of time that the criteria for response per RECIST are first met until disease progression
measure: Overall Survival (OS)
timeFrame: Date of Consent until death, up to 32 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Center
state: California
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Post Falls
country: United States
facility: Kootenai Cancer Center
state: Idaho
city: Niles
country: United States
facility: Oncology Specialists, SC
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Memphis
country: United States
facility: West Clinic
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Northwest Oncology
name: Brian L Samuels, MD
role: STUDY_CHAIR
References: