Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma

Liposarcoma Clinical Trial

Official title:

A Phase II Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01506596
• Other study ID #: ABLSMLS1101
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 6, 2012
• Last updated: December 7, 2015
• Start date: March 2012
• Est. completion date: June 2016

Study information

• Verified date: December 2015
• Source: Vector Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: June 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liposarcoma
• Metastatic Liposarcoma
• Surgically Unresectable Liposarcoma

Intervention

Drug:
• pazopanib
Pazopanib 800 mg orally once daily will be started on Cycle 1 Day 1 and will be administered continuously for a 28-day cycle. Study treatment may continue until disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	West Clinic	Memphis	Tennessee
United States	University of Minnesota	Minneapolis	Minnesota
United States	Oncology Specialists, SC	Niles	Illinois
United States	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania
United States	Kootenai Cancer Center	Post Falls	Idaho
United States	Sarcoma Oncology Center	Santa Monica	California
United States	Washington Cancer Institute	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Vector Oncology	Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12-week Progression Free Rate	Progression will be as defined per Response Evaluation Criteria In Solid Tumors (RECIST) guidelines version 1.1. Subjects who remain under observation and progression free at 12 weeks will be defined as treatment successes. Subjects who progress per RECIST by 12 weeks or who drop out without evidence of progression prior to 12 weeks will be defined as treatment failures.	Assessed after 12 weeks of study treatment	No
Secondary	Progression free survival (PFS)	The time origin for PFS will be Cycle 1 Day 1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 24 months.	Cycle 1 Day 1 until the subject experiences disease progression	No
Secondary	Response rate (RR)	Response is defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1.	Cycle 1 Day 1 until end of study treatment	No
Secondary	Duration of response	Response is defined as Complete Response (CR) or Partial Response (PR) per RECIST v1.1. Repeat radiologic imaging will be conducted after every 3 cycles of treatment (approximately every 12 weeks) to evaluate disease status per RECIST v1.1. Confirmation of CR or PR is required by repeat scans that should be performed 4 weeks after the criteria for response are first met.	Measure of the amount of time that the criteria for response per RECIST are first met until disease progression	No
Secondary	Overall survival (OS)	The time origin for OS will be Cycle 1 Day 1. Subjects will be followed for up to 24 months after the end of treatment or until death, lost to follow-up, or withdrawal of consent, whichever occurs first.	Cycle 1 Day 1 up to 24 months after the end of study treatment	No