Patient case: 26-year-old male with Liposarcoma. Genetic variant: MDM2 Amplification. Other conditions: None.

Clinical trial: Study of Pazopanib in the Treatment of Surgically Unresectable or Metastatic Liposarcoma

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: 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.

Relevance to patient case: not relevant