Study of Pazopanib in the Treatment of Osteosarcoma Metastatic to the Lung

• Status: Terminated
• Trial end date: 2017-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the 4-month Progression-Free Survival (PFS), with demonstrated increase in tumor doubling time, of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: George Clinical Pty Ltd; Vector Oncology
• Collaborators: GlaxoSmithKline; Novartis

Criteria

Inclusion Criteria:

• Written informed consent or assent

• Age > or = to 16 years

• Histologically confirmed diagnosis of osteosarcoma with lung metastasis, who have progressed on the prior line of therapy, or relapsed

• Ineligible for curative pulmonary metastasectomy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. At least one measurable lesion must be in the lungs.

• Eligible subjects are required to have > or = to 1 line of multi-agent chemotherapy either neoadjuvantly or adjuvantly. Subjects may have had 0-2 lines of therapy for metastatic disease.

• Measured cardiac ejection fraction > or = to 50% or the institutional lower limit of normal by echocardiogram or MUGA scan.

• Adequate organ system function.

• Females must be either non-child bearing potential or have a negative pregnancy test within 3 to 5 days prior to the first dose of study drug.

Exclusion Criteria:

• Children not in the care or custody of a biological parent, adoptive parent, appointed legal guardian, or legally appointed foster care.

• Prior exposure to VEGFR tyrosine kinase inhibitor (small molecule or antibody) or VEGFR antibody.

• 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 (CNS) 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 abnormalities that may increase the risk for gastrointestinal bleeding.

• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product.

• Presence of uncontrolled infection.

• Corrected QT interval (QTc) > 480 msecs using Bazett's formula.

• History of certain cardiovascular conditions within the past 6 months.

• Class II-IV congestive heart failure, as defined by the New York Heart Association

• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].

• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

• Prior major surgery or trauma within 28 days prior to the protocol-mandated 4-week drug holiday 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 of red blood in excess of 2.5 mL (or one half teaspoon) 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/assent, 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 the study treatment.

• Radiation therapy, minor surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days prior to the protocol-mandated 4-week drug holiday.

• Administration of any non-oncologic investigational drug within 30 days or five half-lives (whichever is longer) prior to the protocol-mandated 4-week drug holiday.

• 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 or idiosyncrasy to drugs chemically related to pazopanib or excipients that contraindicates participation.

• An untreated tumor growth rate of < 6.1% during the Screening period may exclude some patients.